Mitochondrial STAT3 and reactive oxygen species: a fulcrum of adipogenesis?
- Kramer, Adam H, Kadye, Rose, Houseman, Pascalene S, Prinsloo, Earl
- Authors: Kramer, Adam H , Kadye, Rose , Houseman, Pascalene S , Prinsloo, Earl
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431674 , vital:72795 , xlink:href="https://doi.org/10.1080/21623996.2015.1084084"
- Description: The balance between cellular lineages can be controlled by reactive oxygen species (ROS). Cellular differentiation into adipocytes is highly dependent on the production of ROS to initiate the process through activation of multiple interlinked factors that stimulate mitotic clonal expansion and cellular maturation. The signal transducer and activator of transcription family of signaling proteins have accepted roles in adipogenesis and associated lipogenesis. Non-canonical mitochondrial localization of STAT3 and other members of the STAT family however opens up new avenues for investigation of its role in the aforementioned processes. Following recent observations of differences in mitochondrially localized serine 727 phosphorylated STAT3 (mtSTAT3-pS727) in preadipocytes and adipocytes, here, we hypothesize and speculate further on the role of mitochondrial STAT3 in adipogenesis.
- Full Text:
- Date Issued: 2015
- Authors: Kramer, Adam H , Kadye, Rose , Houseman, Pascalene S , Prinsloo, Earl
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431674 , vital:72795 , xlink:href="https://doi.org/10.1080/21623996.2015.1084084"
- Description: The balance between cellular lineages can be controlled by reactive oxygen species (ROS). Cellular differentiation into adipocytes is highly dependent on the production of ROS to initiate the process through activation of multiple interlinked factors that stimulate mitotic clonal expansion and cellular maturation. The signal transducer and activator of transcription family of signaling proteins have accepted roles in adipogenesis and associated lipogenesis. Non-canonical mitochondrial localization of STAT3 and other members of the STAT family however opens up new avenues for investigation of its role in the aforementioned processes. Following recent observations of differences in mitochondrially localized serine 727 phosphorylated STAT3 (mtSTAT3-pS727) in preadipocytes and adipocytes, here, we hypothesize and speculate further on the role of mitochondrial STAT3 in adipogenesis.
- Full Text:
- Date Issued: 2015
Guardian of the furnace: mitochondria, TRAP1, ROS and stem cell maintenance
- Kadye, Rose, Kramer, Adam H, Joos-Vandewalle, Julia, Parsons, Michelle, Njengele, Zikhona, Hoppe, Heinrich C, Prinsloo, Earl
- Authors: Kadye, Rose , Kramer, Adam H , Joos-Vandewalle, Julia , Parsons, Michelle , Njengele, Zikhona , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431119 , vital:72745 , xlink:href="https://doi.org/10.1002/iub.1234"
- Description: Mitochondria are key to eukaryotic cell survival and their activity is linked to generation of reactive oxygen species (ROS) which in turn acts as both an intracellular signal and an effective executioner of cells with regards to cellular senescence. The mitochondrial molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1) is often termed the cytoprotective chaperone for its role in cancer cell survival and protection from apoptosis. Here, we hypothesize that TRAP1 serves to modulate mitochondrial activity in stem cell maintenance, survival and differentiation.
- Full Text:
- Date Issued: 2014
- Authors: Kadye, Rose , Kramer, Adam H , Joos-Vandewalle, Julia , Parsons, Michelle , Njengele, Zikhona , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431119 , vital:72745 , xlink:href="https://doi.org/10.1002/iub.1234"
- Description: Mitochondria are key to eukaryotic cell survival and their activity is linked to generation of reactive oxygen species (ROS) which in turn acts as both an intracellular signal and an effective executioner of cells with regards to cellular senescence. The mitochondrial molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1) is often termed the cytoprotective chaperone for its role in cancer cell survival and protection from apoptosis. Here, we hypothesize that TRAP1 serves to modulate mitochondrial activity in stem cell maintenance, survival and differentiation.
- Full Text:
- Date Issued: 2014
Plasmodium falciparum Hop (PfHop) interacts with the Hsp70 chaperone in a nucleotide-dependent fashion and exhibits ligand selectivity
- Zininga, Tawanda, Makumire, Stanley, Gitau, Grace W, Njunge, James M, Pooe, Ofentse J, Klimek, Hanna, Scheurr, Robina, Raifer, Hartmann, Prinsloo, Earl, Przyborski, Jude M, Hoppe, Heinrich C, Shonhai, Addmore
- Authors: Zininga, Tawanda , Makumire, Stanley , Gitau, Grace W , Njunge, James M , Pooe, Ofentse J , Klimek, Hanna , Scheurr, Robina , Raifer, Hartmann , Prinsloo, Earl , Przyborski, Jude M , Hoppe, Heinrich C , Shonhai, Addmore
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431752 , vital:72801 , xlink:href=" https://doi.org/10.1371/journal.pone.0135326"
- Description: Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red blood cells. It is thought that Hsps maintain proteostasis under the unfavourable conditions that malaria parasites encounter in the host environment. Although heat shock protein 70 (Hsp70) is capable of independent folding of some proteins, its functional cooperation with heat shock protein 90 (Hsp90) facilitates folding of some proteins such as kinases and steroid hormone receptors into their fully functional forms. The cooperation of Hsp70 and Hsp90 occurs through an adaptor protein called Hsp70-Hsp90 organising protein (Hop). We previously characterised the Hop protein from Plasmodium falciparum (PfHop). We observed that the protein co-localised with the cytosol-localised chaperones, PfHsp70-1 and PfHsp90 at the blood stages of the malaria parasite. In the current study, we demonstrated that PfHop is a stress-inducible protein. We further explored the direct interaction between PfHop and PfHsp70-1 using far Western and surface plasmon resonance (SPR) analyses.
- Full Text:
- Date Issued: 2015
- Authors: Zininga, Tawanda , Makumire, Stanley , Gitau, Grace W , Njunge, James M , Pooe, Ofentse J , Klimek, Hanna , Scheurr, Robina , Raifer, Hartmann , Prinsloo, Earl , Przyborski, Jude M , Hoppe, Heinrich C , Shonhai, Addmore
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431752 , vital:72801 , xlink:href=" https://doi.org/10.1371/journal.pone.0135326"
- Description: Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red blood cells. It is thought that Hsps maintain proteostasis under the unfavourable conditions that malaria parasites encounter in the host environment. Although heat shock protein 70 (Hsp70) is capable of independent folding of some proteins, its functional cooperation with heat shock protein 90 (Hsp90) facilitates folding of some proteins such as kinases and steroid hormone receptors into their fully functional forms. The cooperation of Hsp70 and Hsp90 occurs through an adaptor protein called Hsp70-Hsp90 organising protein (Hop). We previously characterised the Hop protein from Plasmodium falciparum (PfHop). We observed that the protein co-localised with the cytosol-localised chaperones, PfHsp70-1 and PfHsp90 at the blood stages of the malaria parasite. In the current study, we demonstrated that PfHop is a stress-inducible protein. We further explored the direct interaction between PfHop and PfHsp70-1 using far Western and surface plasmon resonance (SPR) analyses.
- Full Text:
- Date Issued: 2015
Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion
- Ziningwa, Tawanda, Achilonu, Ikechukwu, Hoppe, Heinrich C, Prinsloo, Earl, Dirr, Heinrich W, Shonhai, Addmore
- Authors: Ziningwa, Tawanda , Achilonu, Ikechukwu , Hoppe, Heinrich C , Prinsloo, Earl , Dirr, Heinrich W , Shonhai, Addmore
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431765 , vital:72802 , xlink:href="https://doi.org/10.1007/s12192-016-0678-4"
- Description: The role of molecular chaperones, among them heat shock proteins (Hsps), in the development of malaria parasites has been well documented. Hsp70s are molecular chaperones that facilitate protein folding. Hsp70 proteins are composed of an N-terminal nucleotide binding domain (NBD), which confers them with ATPase activity and a Cterminal substrate binding domain (SBD). In the ADPbound state, Hsp70 possesses high affinity for substrate and releases the folded substrate when it is bound to ATP. The two domains are connected by a conserved linker segment. Hsp110 proteins possess an extended lid segment, a feature that distinguishes them from canonical Hsp70s.
- Full Text:
- Date Issued: 2016
- Authors: Ziningwa, Tawanda , Achilonu, Ikechukwu , Hoppe, Heinrich C , Prinsloo, Earl , Dirr, Heinrich W , Shonhai, Addmore
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431765 , vital:72802 , xlink:href="https://doi.org/10.1007/s12192-016-0678-4"
- Description: The role of molecular chaperones, among them heat shock proteins (Hsps), in the development of malaria parasites has been well documented. Hsp70s are molecular chaperones that facilitate protein folding. Hsp70 proteins are composed of an N-terminal nucleotide binding domain (NBD), which confers them with ATPase activity and a Cterminal substrate binding domain (SBD). In the ADPbound state, Hsp70 possesses high affinity for substrate and releases the folded substrate when it is bound to ATP. The two domains are connected by a conserved linker segment. Hsp110 proteins possess an extended lid segment, a feature that distinguishes them from canonical Hsp70s.
- Full Text:
- Date Issued: 2016
Overexpression, Purification and Characterisation of the Plasmodium falciparum Hsp70-z (PfHsp70-z) Protein
- Zininga, Tawanda, Achilonu, Ikechukwu, Hoppe, Heinrich C, Prinsloo, Earl, Dirr, Heinrich W, Shonhai, Addmore
- Authors: Zininga, Tawanda , Achilonu, Ikechukwu , Hoppe, Heinrich C , Prinsloo, Earl , Dirr, Heinrich W , Shonhai, Addmore
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431719 , vital:72799 , xlink:href="https://doi.org/10.1371/journal.pone.0129445"
- Description: Six Hsp70-like genes are represented on the genome of Plasmodium falciparum. Of these two occur in the cytosol: P. falciparum Hsp70-z (PfHsp70-z) and PfHsp70-1. PfHsp70-1 is a well characterised canonical Hsp70 that facilitates protein quality control and is crucial for the development of malaria parasites. There is very little known about PfHsp70-z. However, PfHsp70-z is known to be essential and is implicated in suppressing aggregation of asparagine-rich proteins of P. falciparum. In addition, its expression at the clinical stage of malaria correlates with disease prognosis. Based on structural evidence PfHsp70-z belongs to the Hsp110 family of proteins. Since Hsp110 proteins have been described as nucleotide exchange factors (NEFs) of their canonical Hsp70 counterparts, it has been speculated that PfHsp70-z may serve as a NEF of PfHsp70-1. In the current study, P. falciparum cells cultured in vitro were subjected to heat stress, triggering the enhanced expression of PfHsp70-z. Biochemical assays conducted using recombinant PfHsp70-z protein demonstrated that the protein is heat stable and possesses ATPase activity. Furthermore, we observed that PfHsp70-z is capable of self-association. The structural-functional features of PfHsp70-z provide further evidence for its role as a chaperone and possible nucleotide exchange factor of PfHsp70-1.
- Full Text:
- Date Issued: 2015
- Authors: Zininga, Tawanda , Achilonu, Ikechukwu , Hoppe, Heinrich C , Prinsloo, Earl , Dirr, Heinrich W , Shonhai, Addmore
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431719 , vital:72799 , xlink:href="https://doi.org/10.1371/journal.pone.0129445"
- Description: Six Hsp70-like genes are represented on the genome of Plasmodium falciparum. Of these two occur in the cytosol: P. falciparum Hsp70-z (PfHsp70-z) and PfHsp70-1. PfHsp70-1 is a well characterised canonical Hsp70 that facilitates protein quality control and is crucial for the development of malaria parasites. There is very little known about PfHsp70-z. However, PfHsp70-z is known to be essential and is implicated in suppressing aggregation of asparagine-rich proteins of P. falciparum. In addition, its expression at the clinical stage of malaria correlates with disease prognosis. Based on structural evidence PfHsp70-z belongs to the Hsp110 family of proteins. Since Hsp110 proteins have been described as nucleotide exchange factors (NEFs) of their canonical Hsp70 counterparts, it has been speculated that PfHsp70-z may serve as a NEF of PfHsp70-1. In the current study, P. falciparum cells cultured in vitro were subjected to heat stress, triggering the enhanced expression of PfHsp70-z. Biochemical assays conducted using recombinant PfHsp70-z protein demonstrated that the protein is heat stable and possesses ATPase activity. Furthermore, we observed that PfHsp70-z is capable of self-association. The structural-functional features of PfHsp70-z provide further evidence for its role as a chaperone and possible nucleotide exchange factor of PfHsp70-1.
- Full Text:
- Date Issued: 2015
Supplementary Material Synthesis and biological evaluation of (E)-cinnamic acid,(E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl) vinyl] thiazole derivatives
- Olawode, Emmanuel O, Tandlich, Roman, Prinsloo, Earl, Isaacs, Michelle, Hoppe, Heinrich C, Seldon, Ronnett, Warner, Digby F, Steenkamp, Vanessa, Kaye, Perry T
- Authors: Olawode, Emmanuel O , Tandlich, Roman , Prinsloo, Earl , Isaacs, Michelle , Hoppe, Heinrich C , Seldon, Ronnett , Warner, Digby F , Steenkamp, Vanessa , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431778 , vital:72803 , xlink:href=" https://www.arkat-usa.org/get-file/59868/"
- Description: The screening was conducted using multi-well plates which are suited for HeLa cells in the log phase of growth with final cell density > 10 cells/cm. Each experiment normally includes a blank control, containing medium without the cells.28,45 Non-contaminated HeLa cells (6.57 x 105 cells per well) in media were allowed to grow in the incubator under an atmosphere of 5% CO2 at 37 0C for 24 h. To each well was dispensed 200 µL of HeLa culture, containing 6.57 x 105 cells under LabEAir laminar flow hood (Vivid Air, South Africa); 20 µL of resazurin dye (Sigma TOX-8) and test compound (50 µL) were added, which were then incubated in the presence of 5% CO2 at 37 0C for 24 hours in a shaker, to enhance the distribution of the dye. The absorbance of each well was measured with Bio-tek Power Wave X fluorometer (Beijing, China), and increases in fluorescence was monitored at a wavelength of 590 nm, using an excitation wavelength of 560 nm.
- Full Text:
- Date Issued: 2016
- Authors: Olawode, Emmanuel O , Tandlich, Roman , Prinsloo, Earl , Isaacs, Michelle , Hoppe, Heinrich C , Seldon, Ronnett , Warner, Digby F , Steenkamp, Vanessa , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431778 , vital:72803 , xlink:href=" https://www.arkat-usa.org/get-file/59868/"
- Description: The screening was conducted using multi-well plates which are suited for HeLa cells in the log phase of growth with final cell density > 10 cells/cm. Each experiment normally includes a blank control, containing medium without the cells.28,45 Non-contaminated HeLa cells (6.57 x 105 cells per well) in media were allowed to grow in the incubator under an atmosphere of 5% CO2 at 37 0C for 24 h. To each well was dispensed 200 µL of HeLa culture, containing 6.57 x 105 cells under LabEAir laminar flow hood (Vivid Air, South Africa); 20 µL of resazurin dye (Sigma TOX-8) and test compound (50 µL) were added, which were then incubated in the presence of 5% CO2 at 37 0C for 24 hours in a shaker, to enhance the distribution of the dye. The absorbance of each well was measured with Bio-tek Power Wave X fluorometer (Beijing, China), and increases in fluorescence was monitored at a wavelength of 590 nm, using an excitation wavelength of 560 nm.
- Full Text:
- Date Issued: 2016
Hsp90 binds directly to fibronectin (FN) and inhibition reduces the extracellular fibronectin matrix in breast cancer cells
- Hunter, Morgan C, O’Hagan, Kyle L, Kenyon, Amy, Dhanani, Karim C H, Prinsloo, Earl, Edkins, Adrienne L
- Authors: Hunter, Morgan C , O’Hagan, Kyle L , Kenyon, Amy , Dhanani, Karim C H , Prinsloo, Earl , Edkins, Adrienne L
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431143 , vital:72748 , xlink:href="https://doi.org/10.1371/journal.pone.0086842"
- Description: Heat shock protein 90 (Hsp90) has been identified in the extracellular space and has been shown to chaperone a finite number of extracellular proteins involved in cell migration and invasion. We used chemical cross-linking and immunoprecipitation followed by tandem mass spectrometry (MS/MS) to isolate a complex containing Hsp90 and the matrix protein fibronectin (FN) from breast cancer cells. Further analysis showed direct binding of Hsp90 to FN using an in vitro co-immunoprecipitation assay, a solid phase binding assay and surface plasmon resonance (SPR) spectroscopy. Confocal microscopy showed regions of co-localisation of Hsp90 and FN in breast cancer cell lines. Exogenous Hsp90β was shown to increase the formation of extracellular FN matrix in the Hs578T cell line, whilst knockdown or inhibition of Hsp90 led to a reduction in the levels of both soluble and insoluble FN and could be partially rescued by addition of exogenous Hsp90β. Treatment of cells with novobiocin led to internalization of FN into vesicles that were positive for the presence of the lysosomal marker, LAMP-1. Taken together, the direct interaction between FN and Hsp90, as well as the decreased levels of both soluble and insoluble FN upon Hsp90 inhibition or knockdown, suggested that FN may be a new client protein for Hsp90 and that Hsp90 was involved in FN matrix assembly and/or stability. The identification of FN as a putative client protein of Hsp90 suggests a role for Hsp90 in FN matrix stability, which is important for a number of fundamental cellular processes including embryogenesis, wound healing, cell migration and metastasis.
- Full Text:
- Date Issued: 2014
- Authors: Hunter, Morgan C , O’Hagan, Kyle L , Kenyon, Amy , Dhanani, Karim C H , Prinsloo, Earl , Edkins, Adrienne L
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431143 , vital:72748 , xlink:href="https://doi.org/10.1371/journal.pone.0086842"
- Description: Heat shock protein 90 (Hsp90) has been identified in the extracellular space and has been shown to chaperone a finite number of extracellular proteins involved in cell migration and invasion. We used chemical cross-linking and immunoprecipitation followed by tandem mass spectrometry (MS/MS) to isolate a complex containing Hsp90 and the matrix protein fibronectin (FN) from breast cancer cells. Further analysis showed direct binding of Hsp90 to FN using an in vitro co-immunoprecipitation assay, a solid phase binding assay and surface plasmon resonance (SPR) spectroscopy. Confocal microscopy showed regions of co-localisation of Hsp90 and FN in breast cancer cell lines. Exogenous Hsp90β was shown to increase the formation of extracellular FN matrix in the Hs578T cell line, whilst knockdown or inhibition of Hsp90 led to a reduction in the levels of both soluble and insoluble FN and could be partially rescued by addition of exogenous Hsp90β. Treatment of cells with novobiocin led to internalization of FN into vesicles that were positive for the presence of the lysosomal marker, LAMP-1. Taken together, the direct interaction between FN and Hsp90, as well as the decreased levels of both soluble and insoluble FN upon Hsp90 inhibition or knockdown, suggested that FN may be a new client protein for Hsp90 and that Hsp90 was involved in FN matrix assembly and/or stability. The identification of FN as a putative client protein of Hsp90 suggests a role for Hsp90 in FN matrix stability, which is important for a number of fundamental cellular processes including embryogenesis, wound healing, cell migration and metastasis.
- Full Text:
- Date Issued: 2014
Real-time monitoring of 3T3-L1 preadipocyte differentiation using a commercially available electric cell-substrate impedance sensor system
- Kramer, Adam H, Joos-Vandewalle, Julia, Edkins, Adrienne L, Frost, Carminita L, Prinsloo, Earl
- Authors: Kramer, Adam H , Joos-Vandewalle, Julia , Edkins, Adrienne L , Frost, Carminita L , Prinsloo, Earl
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431171 , vital:72751 , xlink:href="https://doi.org/10.1016/j.bbrc.2013.12.123"
- Description: Real-time analysis offers multiple benefits over traditional end point assays. Here, we present a method of monitoring the optimisation of the growth and differentiation of murine 3T3-L1 preadipocytes to adipocytes using the commercially available ACEA xCELLigence Real-Time Cell Analyser Single Plate (RTCA SP) system. Our findings indicate that the ACEA xCELLigence RTCA SP can reproducibly monitor the primary morphological changes in pre- and post-confluent 3T3-L1 fibroblasts induced to differentiate using insulin, dexamethasone, 3-isobutyl-1-methylxanthine and rosiglitazone; and may be a viable primary method of screening compounds for adipogenic factors.
- Full Text:
- Date Issued: 2014
- Authors: Kramer, Adam H , Joos-Vandewalle, Julia , Edkins, Adrienne L , Frost, Carminita L , Prinsloo, Earl
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431171 , vital:72751 , xlink:href="https://doi.org/10.1016/j.bbrc.2013.12.123"
- Description: Real-time analysis offers multiple benefits over traditional end point assays. Here, we present a method of monitoring the optimisation of the growth and differentiation of murine 3T3-L1 preadipocytes to adipocytes using the commercially available ACEA xCELLigence Real-Time Cell Analyser Single Plate (RTCA SP) system. Our findings indicate that the ACEA xCELLigence RTCA SP can reproducibly monitor the primary morphological changes in pre- and post-confluent 3T3-L1 fibroblasts induced to differentiate using insulin, dexamethasone, 3-isobutyl-1-methylxanthine and rosiglitazone; and may be a viable primary method of screening compounds for adipogenic factors.
- Full Text:
- Date Issued: 2014
The in vitro photo-sonodynamic combinatorial therapy activity of cationic and zwitterionic phthalocyanines on MCF-7 and HeLa cancer cell lines
- Nene, Lindokuhle Cindy, Buthelezi, Khanyisile, Prinsloo, Earl, Nyokong, Tebello
- Authors: Nene, Lindokuhle Cindy , Buthelezi, Khanyisile , Prinsloo, Earl , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/295891 , vital:57387 , xlink:href="https://doi.org/10.1016/j.jphotochem.2022.114116"
- Description: The syntheses and characterization studies of zwitterionic 2,9,16,23-tetrakis-(N-propane sultone-morpholino) zinc(II) (4) and 2,9,16,23-tetrakis-(2,5-dimethyl-4-(N-propane sultone-morpholinomethyl))-phenoxy zinc(II) (6) phthalocyanines are reported in this work. The photophysical properties, reactive oxygen species (ROS) generation and in vitro anticancer photodynamic (PDT), sonodynamic (SDT), and photo-sonodynamic combination (PSDT) therapy activities of the Pcs were studied and compared to their cationic counterparts: (2,9,16,23-tetrakis-(N-methyl-morpholino) Zn(II)Pc, 3), (2,9,16,23-tetrakis-(2,5-dimethyl-4-(N-methylmorpholine)-phenoxy) Zn(II)Pc, 5). The cationic Pcs maintained higher anticancer activity for all treatment types and had higher ROS generation compared to the zwitterionic Pcs. Singlet oxygen and hydroxyl radicals were generated during ultrasound and combination irradiations of the Pcs. The zwitterionic Pcs also generated carbon radicals under ultrasound and combination irradiations. The ability of the Pcs to generate ROS is essential for PDT, SDT and PSDT, thus making these Pcs potential anticancer probes for these treatment types. Furthermore, the Pcs demonstrated the ability to bind to bovine serum albumin protein.
- Full Text:
- Date Issued: 2022
- Authors: Nene, Lindokuhle Cindy , Buthelezi, Khanyisile , Prinsloo, Earl , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/295891 , vital:57387 , xlink:href="https://doi.org/10.1016/j.jphotochem.2022.114116"
- Description: The syntheses and characterization studies of zwitterionic 2,9,16,23-tetrakis-(N-propane sultone-morpholino) zinc(II) (4) and 2,9,16,23-tetrakis-(2,5-dimethyl-4-(N-propane sultone-morpholinomethyl))-phenoxy zinc(II) (6) phthalocyanines are reported in this work. The photophysical properties, reactive oxygen species (ROS) generation and in vitro anticancer photodynamic (PDT), sonodynamic (SDT), and photo-sonodynamic combination (PSDT) therapy activities of the Pcs were studied and compared to their cationic counterparts: (2,9,16,23-tetrakis-(N-methyl-morpholino) Zn(II)Pc, 3), (2,9,16,23-tetrakis-(2,5-dimethyl-4-(N-methylmorpholine)-phenoxy) Zn(II)Pc, 5). The cationic Pcs maintained higher anticancer activity for all treatment types and had higher ROS generation compared to the zwitterionic Pcs. Singlet oxygen and hydroxyl radicals were generated during ultrasound and combination irradiations of the Pcs. The zwitterionic Pcs also generated carbon radicals under ultrasound and combination irradiations. The ability of the Pcs to generate ROS is essential for PDT, SDT and PSDT, thus making these Pcs potential anticancer probes for these treatment types. Furthermore, the Pcs demonstrated the ability to bind to bovine serum albumin protein.
- Full Text:
- Date Issued: 2022
Synthesis of a near infrared-actuated phthalocyanine-lipid vesicle system for augmented photodynamic therapy
- Nwahara, Namdi, Managa, Muthumuni, Stoffels, Mihlali, Britton, Jonathan, Prinsloo, Earl, Nyokong, Tebello
- Authors: Nwahara, Namdi , Managa, Muthumuni , Stoffels, Mihlali , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/185395 , vital:44383 , xlink:href="https://doi.org/10.1016/j.synthmet.2021.116811"
- Description: The efficacy of photodynamic therapy (PDT) is often limited by the poor bio-distributive properties of conventional photosensitizers and the local hypoxic microenvironment that characterises most solid tumours. Herein, a novel in situ oxygenic lipid formulation for photodynamic therapy (PDT) is reported. Such a hybrid was synthesized by adsorbing bimetallic nanozyme, MnO2@PtNPs (NPs = nanoparticles) onto graphene quantum dots (GQDs) – zinc (II) phthalocyanine conjugates, followed by liposomal encapsulation, affording it enhanced water solubility. The MnO2@PtNPs, which are is shown to possess excellent catalase-like properties surpassing that of MnO2 or PtNPs alone, serves to catalyze H2O2 to O2, while the zinc (II) phthalocyanine (1) serves to transform the formed oxygen to generate cytotoxic singlet oxygen immediately. We show that by combining each function of the respective building blocks, the as-synthesized 1-GQDs-MnO2@PtNPs-liposomes not only maintains the properties of oxygen supplementation through H2O2 catalysis but also displays cooperative properties for enhanced singlet oxygen production. Consequently, a remarkably improved PDT efficacy was observed for 1-GQDs-MnO2@PtNPs-liposomes in both normoxia and hypoxia. These results demonstrate the potential applicability of such nanozyme constituted 1-GQDs-MnO2@PtNPs-liposomes for achieving tumour treatment in hypoxic conditions by PDT.
- Full Text:
- Date Issued: 2021
- Authors: Nwahara, Namdi , Managa, Muthumuni , Stoffels, Mihlali , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/185395 , vital:44383 , xlink:href="https://doi.org/10.1016/j.synthmet.2021.116811"
- Description: The efficacy of photodynamic therapy (PDT) is often limited by the poor bio-distributive properties of conventional photosensitizers and the local hypoxic microenvironment that characterises most solid tumours. Herein, a novel in situ oxygenic lipid formulation for photodynamic therapy (PDT) is reported. Such a hybrid was synthesized by adsorbing bimetallic nanozyme, MnO2@PtNPs (NPs = nanoparticles) onto graphene quantum dots (GQDs) – zinc (II) phthalocyanine conjugates, followed by liposomal encapsulation, affording it enhanced water solubility. The MnO2@PtNPs, which are is shown to possess excellent catalase-like properties surpassing that of MnO2 or PtNPs alone, serves to catalyze H2O2 to O2, while the zinc (II) phthalocyanine (1) serves to transform the formed oxygen to generate cytotoxic singlet oxygen immediately. We show that by combining each function of the respective building blocks, the as-synthesized 1-GQDs-MnO2@PtNPs-liposomes not only maintains the properties of oxygen supplementation through H2O2 catalysis but also displays cooperative properties for enhanced singlet oxygen production. Consequently, a remarkably improved PDT efficacy was observed for 1-GQDs-MnO2@PtNPs-liposomes in both normoxia and hypoxia. These results demonstrate the potential applicability of such nanozyme constituted 1-GQDs-MnO2@PtNPs-liposomes for achieving tumour treatment in hypoxic conditions by PDT.
- Full Text:
- Date Issued: 2021
Sn (IV) porphyrin-biotin decorated nitrogen doped graphene quantum dots nanohybrids for photodynamic therapy
- Magaela, N Bridged, Matshitse, Refilwe, Balaji, Babu, Managa, Muthumuni, Prinsloo, Earl, Nyokong, Tebello
- Authors: Magaela, N Bridged , Matshitse, Refilwe , Balaji, Babu , Managa, Muthumuni , Prinsloo, Earl , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/230018 , vital:49733 , xlink:href="https://doi.org/10.1016/j.poly.2021.115624"
- Description: Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure for cancer treatment. This study focuses on the synthesis, photophysicochemical properties, and PDT activity of Sn (IV) porphyrin (2), when linked to biotin decorated nitrogen doped graphene quantum dots (B-NGQDs). The porphyrin complex 2 was conjugated through an ester bond to B-NGQDs to form 2-B-NGQDs. Singlet oxygen quantum yield increased for 2 when linked to B-NGQDs to form 2-B-NQGDs. The dark toxicity and photodynamic therapy studies were conducted for 2, NGQDs and their conjugates using MCF-7 breast cancer cells. The cell viability for dark toxicity of all the compounds was above 90%, and 2-B-NGQDs showed high PDT activity at a concentration of 40 µg/mL with cell viability of 22%.
- Full Text:
- Date Issued: 2022
- Authors: Magaela, N Bridged , Matshitse, Refilwe , Balaji, Babu , Managa, Muthumuni , Prinsloo, Earl , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/230018 , vital:49733 , xlink:href="https://doi.org/10.1016/j.poly.2021.115624"
- Description: Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure for cancer treatment. This study focuses on the synthesis, photophysicochemical properties, and PDT activity of Sn (IV) porphyrin (2), when linked to biotin decorated nitrogen doped graphene quantum dots (B-NGQDs). The porphyrin complex 2 was conjugated through an ester bond to B-NGQDs to form 2-B-NGQDs. Singlet oxygen quantum yield increased for 2 when linked to B-NGQDs to form 2-B-NQGDs. The dark toxicity and photodynamic therapy studies were conducted for 2, NGQDs and their conjugates using MCF-7 breast cancer cells. The cell viability for dark toxicity of all the compounds was above 90%, and 2-B-NGQDs showed high PDT activity at a concentration of 40 µg/mL with cell viability of 22%.
- Full Text:
- Date Issued: 2022
Photodynamic activity of 2, 6-dibrominated dimethylaminophenylbuta-1, 3-dienylBODIPY dyes
- Khubeka, Gugu, Babu, Balaji, Prinsloo, Earl, Kobayashi, Nagao, Mack, John, Nyokong, Tebello
- Authors: Khubeka, Gugu , Babu, Balaji , Prinsloo, Earl , Kobayashi, Nagao , Mack, John , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/190804 , vital:45030 , xlink:href="https://doi.org/10.1142/S1088424620500509"
- Description: Mono- and disubstituted 2,6-dibromo-dimethylaminophenylbuta-1,3-dienylBODIPY dyes were successfully prepared, and their in vitro photodynamic activities against MCF-7 breast cancer cells were evaluated with a Thorlabs M660L4 660 nm LED (336 J · cm−2)−2). The IC5050 value of the monophenylbuta-1,3-dienylBODIPY was ca. 2.1 μμM, while that of the diphenylbuta-1,3-dienylBODIPY was > 50 μμM. Both dyes exhibited minimal dark toxicity. The results demonstrate that monosubstituted 2,6-dibromo-dimethylaminophenylbuta-1,3-dienylBODIPY dyes merit further in-depth study for use as photosensitizer dyes in photodynamic therapy.
- Full Text:
- Date Issued: 2021
- Authors: Khubeka, Gugu , Babu, Balaji , Prinsloo, Earl , Kobayashi, Nagao , Mack, John , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/190804 , vital:45030 , xlink:href="https://doi.org/10.1142/S1088424620500509"
- Description: Mono- and disubstituted 2,6-dibromo-dimethylaminophenylbuta-1,3-dienylBODIPY dyes were successfully prepared, and their in vitro photodynamic activities against MCF-7 breast cancer cells were evaluated with a Thorlabs M660L4 660 nm LED (336 J · cm−2)−2). The IC5050 value of the monophenylbuta-1,3-dienylBODIPY was ca. 2.1 μμM, while that of the diphenylbuta-1,3-dienylBODIPY was > 50 μμM. Both dyes exhibited minimal dark toxicity. The results demonstrate that monosubstituted 2,6-dibromo-dimethylaminophenylbuta-1,3-dienylBODIPY dyes merit further in-depth study for use as photosensitizer dyes in photodynamic therapy.
- Full Text:
- Date Issued: 2021
Folic acid-modified phthalocyanine-nanozyme loaded liposomes for targeted photodynamic therapy
- Nwahara, Nnamdi, Abrahams, Garth, Prinsloo, Earl, Nyokong, Tebello
- Authors: Nwahara, Nnamdi , Abrahams, Garth , Prinsloo, Earl , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/231369 , vital:49881 , xlink:href="https://doi.org/10.1016/j.pdpdt.2021.102527"
- Description: The hypoxic tumour microenvironment and poor spatiotemporal localization of photosensitizers are two significant obstacles that limit practical applications of photodynamic therapy. In response, a biocompatible, light-activatable liposome integrated with both a zinc phthalocyanine photodynamic component and Pt nanoparticles-decorated with MnO2 catalase-mimicking component are engineered. This multifunctional system was rationally designed using unsaturated phospholipids to achieve on-demand drug release following light irradiation. Specificity was achieved by folic acid functionalization resulting in folate-modified liposomes (FTLiposomes). We demonstrated its specific uptake by fluorescence imaging using folate receptor (FR) overexpressing HeLa and MCF-7 cells as in vitro models. This multifunctional liposome exhibits superior hypoxic anti-tumour effects and holds the potential to reduce side effects associated with untargeted therapy. Fluorescence of the constituent ZnPc and folate-receptor targeting could enable tracking and permit spatiotemporal regulation for improved cancer treatment.
- Full Text:
- Date Issued: 2021
- Authors: Nwahara, Nnamdi , Abrahams, Garth , Prinsloo, Earl , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/231369 , vital:49881 , xlink:href="https://doi.org/10.1016/j.pdpdt.2021.102527"
- Description: The hypoxic tumour microenvironment and poor spatiotemporal localization of photosensitizers are two significant obstacles that limit practical applications of photodynamic therapy. In response, a biocompatible, light-activatable liposome integrated with both a zinc phthalocyanine photodynamic component and Pt nanoparticles-decorated with MnO2 catalase-mimicking component are engineered. This multifunctional system was rationally designed using unsaturated phospholipids to achieve on-demand drug release following light irradiation. Specificity was achieved by folic acid functionalization resulting in folate-modified liposomes (FTLiposomes). We demonstrated its specific uptake by fluorescence imaging using folate receptor (FR) overexpressing HeLa and MCF-7 cells as in vitro models. This multifunctional liposome exhibits superior hypoxic anti-tumour effects and holds the potential to reduce side effects associated with untargeted therapy. Fluorescence of the constituent ZnPc and folate-receptor targeting could enable tracking and permit spatiotemporal regulation for improved cancer treatment.
- Full Text:
- Date Issued: 2021
A comparative study of the photophysicochemical and photodynamic activity properties of meso-4-methylthiophenyl functionalized Sn (IV) tetraarylporphyrins and triarylcorroles
- Dingiswayo, Somila, Babu, Balaji, Prinsloo, Earl, Mack, John, Nyokong, Tebello
- Authors: Dingiswayo, Somila , Babu, Balaji , Prinsloo, Earl , Mack, John , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186157 , vital:44469 , xlink:href="https://doi.org/10.1142/S1088424620500273"
- Description: Tin(IV) complexes of a 4-methylthiophenyl functionalized porphyrin (1-Sn) and its corrole analogue (2-Sn) were synthesized so that their photophysicochemical properties and photodynamic activities against MCF-7 breast cancer cells could be compared. Singlet oxygen luminescence studies revealed that 1-Sn and 2-Sn have comparable ΦΔΦΔ values in DMF of 0.59 and 0.60, respectively, while the IC5050 values after irradiation of MCF-7 cells for 30 min with a Thorlabs 625 nm LED (432 J · cm−2)−2) were determined to be 12.4 and 8.9 μμM. The results demonstrate that the cellular uptake of 2-Sn and its molar absorptivity at the irradiation wavelength play a crucial role during in vitro cytotoxicity studies.
- Full Text:
- Date Issued: 2020
- Authors: Dingiswayo, Somila , Babu, Balaji , Prinsloo, Earl , Mack, John , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186157 , vital:44469 , xlink:href="https://doi.org/10.1142/S1088424620500273"
- Description: Tin(IV) complexes of a 4-methylthiophenyl functionalized porphyrin (1-Sn) and its corrole analogue (2-Sn) were synthesized so that their photophysicochemical properties and photodynamic activities against MCF-7 breast cancer cells could be compared. Singlet oxygen luminescence studies revealed that 1-Sn and 2-Sn have comparable ΦΔΦΔ values in DMF of 0.59 and 0.60, respectively, while the IC5050 values after irradiation of MCF-7 cells for 30 min with a Thorlabs 625 nm LED (432 J · cm−2)−2) were determined to be 12.4 and 8.9 μμM. The results demonstrate that the cellular uptake of 2-Sn and its molar absorptivity at the irradiation wavelength play a crucial role during in vitro cytotoxicity studies.
- Full Text:
- Date Issued: 2020
The photophysicochemical properties and photodynamic therapy activity of phenyldiazenyl phenoxy substituted phthalocyanines when incorporated into Pluronic® F127 micelles
- Motloung, Banele M, Sekhosana, Kutloano E, Managa, Muthumuni, Prinsloo, Earl, Nyokong, Tebello
- Authors: Motloung, Banele M , Sekhosana, Kutloano E , Managa, Muthumuni , Prinsloo, Earl , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186769 , vital:44532 , xlink:href="https://doi.org/10.1016/j.poly.2019.114157"
- Description: The synthesis, photophysicochemical properties and photodynamic activity (PDT) of 4(4-phenyldiazenyl) phenoxy substituted indium (III) (InPc) and zinc (ZnPc) phthalocyanines when alone or incorporated into Pluronic_ F127 micelles are presented in this study. The InPc exhibited higher singlet oxygen (UD) at 0.47 compared to the ZnPc at 0.20 in dimethylsulfoxide. The UD values in the presence of Pluronic_ F127 and in water, were 0.32 for InPc and 0.09 for ZnPc. The triplet quantum yields (UT) were 0.92 for InPc and 0.32 for ZnPc in DMSO. The PDT activity followed the same trend as the singlet oxygen quantum yields. At the highest concentration, InPc in Pluronic_ F127 gave 22% cell viability compared to 34% for complex ZnPc. The partition coefficient Kp values were determined using the water and octanol system. InPc had a larger Kp suggesting that it is more likely to be taken up by the cancer cells, hence it exhibited better PDT activity.
- Full Text:
- Date Issued: 2019
- Authors: Motloung, Banele M , Sekhosana, Kutloano E , Managa, Muthumuni , Prinsloo, Earl , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186769 , vital:44532 , xlink:href="https://doi.org/10.1016/j.poly.2019.114157"
- Description: The synthesis, photophysicochemical properties and photodynamic activity (PDT) of 4(4-phenyldiazenyl) phenoxy substituted indium (III) (InPc) and zinc (ZnPc) phthalocyanines when alone or incorporated into Pluronic_ F127 micelles are presented in this study. The InPc exhibited higher singlet oxygen (UD) at 0.47 compared to the ZnPc at 0.20 in dimethylsulfoxide. The UD values in the presence of Pluronic_ F127 and in water, were 0.32 for InPc and 0.09 for ZnPc. The triplet quantum yields (UT) were 0.92 for InPc and 0.32 for ZnPc in DMSO. The PDT activity followed the same trend as the singlet oxygen quantum yields. At the highest concentration, InPc in Pluronic_ F127 gave 22% cell viability compared to 34% for complex ZnPc. The partition coefficient Kp values were determined using the water and octanol system. InPc had a larger Kp suggesting that it is more likely to be taken up by the cancer cells, hence it exhibited better PDT activity.
- Full Text:
- Date Issued: 2019
Preparation of NIR absorbing axial substituted tin (iv) porphyrins and their photocytotoxic properties
- Babu, Balaji, Amuhaya, Edith K, Oluwole, David O, Prinsloo, Earl, Mack, John, Nyokong, Tebello
- Authors: Babu, Balaji , Amuhaya, Edith K , Oluwole, David O , Prinsloo, Earl , Mack, John , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/234592 , vital:50211 , xlink:href="https://doi.org/10.1039/C8MD00373D"
- Description: Sn(IV) porphyrins ([Sn(IV)TTP(3PyO)2] (5) and [Sn(IV)TPP(3PyO)2] (6) [tetrathienylporphyrin (TTP), tetraphenylporphyrin (TPP), and pyridyloxy (PyO)]) were prepared and characterized and their photocytotoxicity upon irradiation with 625 nm light has been studied. The presence of the 3PyO axial ligands was found to limit the aggregation and enhance the solubility of 5 and 6 in DMF/H2O (1 : 1). The photophysical properties and photodynamic therapy (PDT) activity of the meso-2-thienyl and meso-phenyl-substituted Sn(IV) porphyrins are compared. 5 and 6 were found to be photocytotoxic in MCF-7 cancer cells when irradiated with a Thorlabs M625L3 LED at 625 nm but remained nontoxic in the dark. The PDT activity of Sn(IV) meso-tetra-2-thienylporphyrin 5 was found to be significantly enhanced relative to its analogous tetraphenylporphyrin 6. There is a marked red-shift of the Q00 band of 5 into the therapeutic window due to the meso-2-thienyl rings, and 5 has an unusually high singlet oxygen quantum yield value of 0.83 in DMF. The results demonstrate that readily synthesized axially ligated Sn(IV) meso-arylporphyrins are potentially suitable for use as singlet oxygen photosensitizers in biomedical applications and merit further in depth investigation in this context.
- Full Text:
- Date Issued: 2019
- Authors: Babu, Balaji , Amuhaya, Edith K , Oluwole, David O , Prinsloo, Earl , Mack, John , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/234592 , vital:50211 , xlink:href="https://doi.org/10.1039/C8MD00373D"
- Description: Sn(IV) porphyrins ([Sn(IV)TTP(3PyO)2] (5) and [Sn(IV)TPP(3PyO)2] (6) [tetrathienylporphyrin (TTP), tetraphenylporphyrin (TPP), and pyridyloxy (PyO)]) were prepared and characterized and their photocytotoxicity upon irradiation with 625 nm light has been studied. The presence of the 3PyO axial ligands was found to limit the aggregation and enhance the solubility of 5 and 6 in DMF/H2O (1 : 1). The photophysical properties and photodynamic therapy (PDT) activity of the meso-2-thienyl and meso-phenyl-substituted Sn(IV) porphyrins are compared. 5 and 6 were found to be photocytotoxic in MCF-7 cancer cells when irradiated with a Thorlabs M625L3 LED at 625 nm but remained nontoxic in the dark. The PDT activity of Sn(IV) meso-tetra-2-thienylporphyrin 5 was found to be significantly enhanced relative to its analogous tetraphenylporphyrin 6. There is a marked red-shift of the Q00 band of 5 into the therapeutic window due to the meso-2-thienyl rings, and 5 has an unusually high singlet oxygen quantum yield value of 0.83 in DMF. The results demonstrate that readily synthesized axially ligated Sn(IV) meso-arylporphyrins are potentially suitable for use as singlet oxygen photosensitizers in biomedical applications and merit further in depth investigation in this context.
- Full Text:
- Date Issued: 2019
Synthesis, characterization and photodynamic activity of Sn (iv) triarylcorroles with red-shifted Q bands
- Babu, Balaji, Prinsloo, Earl, Mack, John, Nyokong, Tebello
- Authors: Babu, Balaji , Prinsloo, Earl , Mack, John , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187521 , vital:44668 , xlink:href="https://doi.org/10.1039/C9NJ03391B"
- Description: Two Sn(IV) triarylcorroles were synthesised and characterized. The absorption spectrum of a meso-thien-2-yl substituted tin(IV)corrole (1-Sn) is red shifted compared to its phenyl analogue (2-Sn) and shows no sign of aggregation in solution. 1-Sn and 2-Sn exhibited singlet oxygen quantum yields of 0.87 and 0.54 in DMF, and have a triplet lifetime of 31 and 50 μs, respectively. Time dependent cellular uptake in MCF-7 cells for 1-Sn reached a peak at 24 h, and 1-Sn was found to be more lipophilic than 2-Sn. 1-Sn showed good photo-cytotoxicity on exposure to a Thorlabs 625 nm LED with an IC50 value of 3.2 μM and remained inactive in the dark.
- Full Text:
- Date Issued: 2019
- Authors: Babu, Balaji , Prinsloo, Earl , Mack, John , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187521 , vital:44668 , xlink:href="https://doi.org/10.1039/C9NJ03391B"
- Description: Two Sn(IV) triarylcorroles were synthesised and characterized. The absorption spectrum of a meso-thien-2-yl substituted tin(IV)corrole (1-Sn) is red shifted compared to its phenyl analogue (2-Sn) and shows no sign of aggregation in solution. 1-Sn and 2-Sn exhibited singlet oxygen quantum yields of 0.87 and 0.54 in DMF, and have a triplet lifetime of 31 and 50 μs, respectively. Time dependent cellular uptake in MCF-7 cells for 1-Sn reached a peak at 24 h, and 1-Sn was found to be more lipophilic than 2-Sn. 1-Sn showed good photo-cytotoxicity on exposure to a Thorlabs 625 nm LED with an IC50 value of 3.2 μM and remained inactive in the dark.
- Full Text:
- Date Issued: 2019
Photodynamic activity of 2, 6-diiodo-3, 5-dithienylvinyleneBODIPYs and their folate-functionalized chitosan-coated Pluronic® F-127 micelles on MCF-7 breast cancer cells
- Molupe, Nthabeleng, Babu, Balaji, Oluwole, David O, Prinsloo, Earl, Gai, Lizhi, Shen, Zhen, Mack, John, Nyokong, Tebello
- Authors: Molupe, Nthabeleng , Babu, Balaji , Oluwole, David O , Prinsloo, Earl , Gai, Lizhi , Shen, Zhen , Mack, John , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186222 , vital:44474 , xlink:href="https://doi.org/10.1142/S1088424619501773"
- Description: A 2,6-diiodo-3,5-dithienylvinyleneBODIPY dye was prepared and encapsulated with folate-chitosan capped Pluronic®® F-127 to provide drug delivery systems for photodynamic therapy (PDT). Moderately enhanced singlet oxygen quantum yields were observed for the dye encapsulation complexes in water. The in vitro dark cytotoxicity and photodynamic activity were investigated on the human breast adenocarcinoma (MCF-7) cell line. Minimal dark cytotoxicity was observed for the BODIPY dyes in 5% DMSO and when encapsulated in folate-functionalized chitosan-coated Pluronic®® F-127 micelles, since the cell viability values are consistently greater than 80% over the 0-40 μg⋅mL−1μg⋅mL−1 concentration range. Upon irradiation of the samples, significant cytocidal activity was observed for the encapsulation complex of a 2,6-diiodo-8-dimethylaminophenyl-3,5-dithienylvinyleneBODIPY dye with less than 50% viable cells observed at concentrations ≥20μg⋅mL−1≥20μg⋅mL−1.
- Full Text:
- Date Issued: 2020
- Authors: Molupe, Nthabeleng , Babu, Balaji , Oluwole, David O , Prinsloo, Earl , Gai, Lizhi , Shen, Zhen , Mack, John , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186222 , vital:44474 , xlink:href="https://doi.org/10.1142/S1088424619501773"
- Description: A 2,6-diiodo-3,5-dithienylvinyleneBODIPY dye was prepared and encapsulated with folate-chitosan capped Pluronic®® F-127 to provide drug delivery systems for photodynamic therapy (PDT). Moderately enhanced singlet oxygen quantum yields were observed for the dye encapsulation complexes in water. The in vitro dark cytotoxicity and photodynamic activity were investigated on the human breast adenocarcinoma (MCF-7) cell line. Minimal dark cytotoxicity was observed for the BODIPY dyes in 5% DMSO and when encapsulated in folate-functionalized chitosan-coated Pluronic®® F-127 micelles, since the cell viability values are consistently greater than 80% over the 0-40 μg⋅mL−1μg⋅mL−1 concentration range. Upon irradiation of the samples, significant cytocidal activity was observed for the encapsulation complex of a 2,6-diiodo-8-dimethylaminophenyl-3,5-dithienylvinyleneBODIPY dye with less than 50% viable cells observed at concentrations ≥20μg⋅mL−1≥20μg⋅mL−1.
- Full Text:
- Date Issued: 2020
Photophysicochemical and photodynamic therapy properties of metallophthalocyanines linked to gold speckled silica nanoparticles
- Dube, Edith, Oluwole, David O, Niemuwa, Nwaji, Prinsloo, Earl, Nyokong, Tebello
- Authors: Dube, Edith , Oluwole, David O , Niemuwa, Nwaji , Prinsloo, Earl , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187472 , vital:44657 , xlink:href="https://doi.org/10.1016/j.pdpdt.2019.01.019"
- Description: This work reports on the linkage of 2(3),9(10),16(17),23(24) tetrakis [(benzo[d]thiazol-2-yl phenoxy) phthalocyaninato] zinc(II) (1) and indium(III) chloride (2) to gold speckled silica (GSS) nanoparticles via gold to sulphur (Au-S) and gold to nitrogen (Au-N) self-assembly to form the conjugates: 1-GSS and 2-GSS. The formed conjugates were characterized using microscopic and spectroscopic techniques, and the photophysicochemical properties and photodynamic therapy (PDT) activity against human breast adenocarcinoma cell line (MCF-7 cells) were studied. The conjugates afforded decrease in fluorescence quantum yields with corresponding increase in triplet and singlet oxygen quantum yields when compared to phthalocyanines alone. Singlet oxygen is cytotoxic to cancer cells hence it is important for PDT. The in vitro dark toxicity of complex 2 and 2-GSS against MCF–7 cells showed ≥93% viable cells within concentration ranges of 10–160 μg/mL. 2–GSS showed enhanced PDT activity with less than 50% viable cells at 80 μg/mL as compared to 2 and GSS alone which showed > 60% viable cells within 10–160 μg/mL. The observed improvements in the PDT activity of 2-GSS could be attributed to the high singlet oxygen generation of 2-GSS compared to 2 alone in addition to the phototoxicity of GSS.
- Full Text:
- Date Issued: 2019
- Authors: Dube, Edith , Oluwole, David O , Niemuwa, Nwaji , Prinsloo, Earl , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187472 , vital:44657 , xlink:href="https://doi.org/10.1016/j.pdpdt.2019.01.019"
- Description: This work reports on the linkage of 2(3),9(10),16(17),23(24) tetrakis [(benzo[d]thiazol-2-yl phenoxy) phthalocyaninato] zinc(II) (1) and indium(III) chloride (2) to gold speckled silica (GSS) nanoparticles via gold to sulphur (Au-S) and gold to nitrogen (Au-N) self-assembly to form the conjugates: 1-GSS and 2-GSS. The formed conjugates were characterized using microscopic and spectroscopic techniques, and the photophysicochemical properties and photodynamic therapy (PDT) activity against human breast adenocarcinoma cell line (MCF-7 cells) were studied. The conjugates afforded decrease in fluorescence quantum yields with corresponding increase in triplet and singlet oxygen quantum yields when compared to phthalocyanines alone. Singlet oxygen is cytotoxic to cancer cells hence it is important for PDT. The in vitro dark toxicity of complex 2 and 2-GSS against MCF–7 cells showed ≥93% viable cells within concentration ranges of 10–160 μg/mL. 2–GSS showed enhanced PDT activity with less than 50% viable cells at 80 μg/mL as compared to 2 and GSS alone which showed > 60% viable cells within 10–160 μg/mL. The observed improvements in the PDT activity of 2-GSS could be attributed to the high singlet oxygen generation of 2-GSS compared to 2 alone in addition to the phototoxicity of GSS.
- Full Text:
- Date Issued: 2019
The photophysicochemical properties and photodynamic therapy activity of In and Zn phthalocyanines when incorporated into individual or mixed Pluronic® micelles
- Motloung, Banele M, Babu, Balaji, Prinsloo, Earl, Nyokong, Tebello
- Authors: Motloung, Banele M , Babu, Balaji , Prinsloo, Earl , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186124 , vital:44465 , xlink:href="https://doi.org/10.1016/j.poly.2020.114683"
- Description: The synthesis, photophysicochemical properties and photodynamic activity (PDT) of tetra-pyridyloxy (1,2) and benzothiazole (3, 4) substituted indium (III) (1,3) and zinc (2, 4) phthalocyanines (Pcs) and their incorporation into Pluronic® F127 and Pluronic L121/F127 mixed micelles (the latter for 3 and 4 only) are presented in this study. The InPcs exhibited higher singlet oxygen (ΦΔ) at 0.76 and 0.68 compared to the ZnPc’s at 0.47 and 0.44 in dimethyl sulfoxide. The ΦΔ values in the presence of Pluronic® F127 and in water, were 0.39 and 0.42 for InPcs and 0.23 and 0.37 for ZnPc. The ΦΔ values in the presence of Pluronic F127/L121 mixed micelles for complex 3 and 4 were 0.51 and 0.29 in water. The Kp was determined using the water and octanol system. InPcs had larger Kp values suggesting that they are more likely to be taken up by the cancer cells hence they showed better PDT activity
- Full Text:
- Date Issued: 2020
- Authors: Motloung, Banele M , Babu, Balaji , Prinsloo, Earl , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186124 , vital:44465 , xlink:href="https://doi.org/10.1016/j.poly.2020.114683"
- Description: The synthesis, photophysicochemical properties and photodynamic activity (PDT) of tetra-pyridyloxy (1,2) and benzothiazole (3, 4) substituted indium (III) (1,3) and zinc (2, 4) phthalocyanines (Pcs) and their incorporation into Pluronic® F127 and Pluronic L121/F127 mixed micelles (the latter for 3 and 4 only) are presented in this study. The InPcs exhibited higher singlet oxygen (ΦΔ) at 0.76 and 0.68 compared to the ZnPc’s at 0.47 and 0.44 in dimethyl sulfoxide. The ΦΔ values in the presence of Pluronic® F127 and in water, were 0.39 and 0.42 for InPcs and 0.23 and 0.37 for ZnPc. The ΦΔ values in the presence of Pluronic F127/L121 mixed micelles for complex 3 and 4 were 0.51 and 0.29 in water. The Kp was determined using the water and octanol system. InPcs had larger Kp values suggesting that they are more likely to be taken up by the cancer cells hence they showed better PDT activity
- Full Text:
- Date Issued: 2020