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
Hsp90α/β associates with the GSK3β/axin1/phospho-β-catenin complex in the human MCF-7 epithelial breast cancer model:
- Cooper, Leanne C, Prinsloo, Earl, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Cooper, Leanne C , Prinsloo, Earl , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165096 , vital:41208 , DOI: 10.1016/j.bbrc.2011.08.136
- Description: Hsp90α/β, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90α/β with its client kinases form the framework of multiple signalling networks. GSK3β, a known Hsp90α/β client, mediates β-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-β-catenin to the 26S proteasome. The canonical Wnt/β-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90α/β involvement in Wnt/β-catenin signalling needs clarification. Here, we describe the association of Hsp90α/β with GSK3β, β-catenin, phospho-β-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90α/β, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90α/β modulates the phosphorylation of β-catenin by interaction in common complex with GSK3β/axin1/β-catenin.
- Full Text:
- Date Issued: 2011
- Authors: Cooper, Leanne C , Prinsloo, Earl , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165096 , vital:41208 , DOI: 10.1016/j.bbrc.2011.08.136
- Description: Hsp90α/β, the signal transduction chaperone, maintains intracellular communication in normal, stem, and cancer cells. The well characterised association of Hsp90α/β with its client kinases form the framework of multiple signalling networks. GSK3β, a known Hsp90α/β client, mediates β-catenin phosphorylation as part of a cytoplasmic destruction complex which targets phospho-β-catenin to the 26S proteasome. The canonical Wnt/β-catenin pathway promotes stem cell self-renewal as well as oncogenesis. The degree of Hsp90α/β involvement in Wnt/β-catenin signalling needs clarification. Here, we describe the association of Hsp90α/β with GSK3β, β-catenin, phospho-β-catenin and the molecular scaffold, axin1, in the human MCF-7 epithelial breast cancer cell model using selective inhibition of Hsp90α/β, confocal laser scanning microscopy and immunoprecipitation. Our findings suggest that Hsp90α/β modulates the phosphorylation of β-catenin by interaction in common complex with GSK3β/axin1/β-catenin.
- Full Text:
- Date Issued: 2011
The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x
- Daniyan, Michael O, Boshoff, Aileen, Prinsloo, Earl, Pesce, Eva-Rachele, Blatch, Gregory L
- Authors: Daniyan, Michael O , Boshoff, Aileen , Prinsloo, Earl , Pesce, Eva-Rachele , Blatch, Gregory L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66098 , vital:28901 , https://doi.org/10.1371/journal.pone.0148517
- Description: publisher version , Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentration-dependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria. , This work was supported by grants from the National Research Foundation (NRF) and Medical Research Council (MRC) of South Africa. The ProteOn XPR36 IAS was purchased from a National Nanotechnology Equipment Programme grant from the Department of Science and Technology and the NRF of South Africa. Michael O. Daniyan was a recipient of the Education Trust Fund (ETF) Academic Staff Training and Development (AST and D) scholarship of Obafemi Awolowo University, Ile-Ife, Nigeria and a Rhodes University Council research bursary
- Full Text:
- Date Issued: 2016
- Authors: Daniyan, Michael O , Boshoff, Aileen , Prinsloo, Earl , Pesce, Eva-Rachele , Blatch, Gregory L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66098 , vital:28901 , https://doi.org/10.1371/journal.pone.0148517
- Description: publisher version , Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentration-dependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria. , This work was supported by grants from the National Research Foundation (NRF) and Medical Research Council (MRC) of South Africa. The ProteOn XPR36 IAS was purchased from a National Nanotechnology Equipment Programme grant from the Department of Science and Technology and the NRF of South Africa. Michael O. Daniyan was a recipient of the Education Trust Fund (ETF) Academic Staff Training and Development (AST and D) scholarship of Obafemi Awolowo University, Ile-Ife, Nigeria and a Rhodes University Council research bursary
- Full Text:
- Date Issued: 2016
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
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
A gold–chitosan composite with low symmetry zinc phthalocyanine for enhanced singlet oxygen generation and improved photodynamic therapy activity
- Dube, Edith, Oluwole, David O, Prinsloo, Earl, Nyokong, Tebello
- Authors: Dube, Edith , Oluwole, David O , Prinsloo, Earl , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/233397 , vital:50087 , xlink:href="https://doi.org/10.1039/C8NJ00801A"
- Description: Novel zinc(II) 3-(4-((3,17,23-tris(4-(benzo[d]thiazol-2-yl)phenoxy)phthalocyanine-9-yl)oxy)phenyl)propanoic acid (complex 3) was synthesised. Complex 3 was subsequently reacted with gold nanoparticles (AuNPs), chitosan (CT) and a gold–chitosan (AuCT) hybrid to form 3-AuNPs, 3-CT and 3-AuCT, respectively. The conjugates afforded a decrease in fluorescence quantum yield with a corresponding increase in the triplet and singlet quantum yields compared to complex 3. The in vitro dark cytotoxicity and photodynamic therapy activity (PDT) of complex 3 and 3-AuCT composites were investigated against epithelial breast cancer cells (MCF-7) with both the samples showing minimum dark cytotoxicity. They both accounted for a cell viability of ≥90% at a concentration of ≤59.2 μg mL−1. 3-AuCT showed better PDT activity (compared to 3 alone) with less than 50% viable cells at a concentration of ≥29.6 μg mL−1 making it potentially applicable for PDT. On the other hand, AuCT displayed some activity against cancer cells, probably due to photothermal activity since gold is a light absorber, however it had more than 50% viable cells at a concentration of ≤59.2 μg mL−1.
- Full Text:
- Date Issued: 2018
- Authors: Dube, Edith , Oluwole, David O , Prinsloo, Earl , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/233397 , vital:50087 , xlink:href="https://doi.org/10.1039/C8NJ00801A"
- Description: Novel zinc(II) 3-(4-((3,17,23-tris(4-(benzo[d]thiazol-2-yl)phenoxy)phthalocyanine-9-yl)oxy)phenyl)propanoic acid (complex 3) was synthesised. Complex 3 was subsequently reacted with gold nanoparticles (AuNPs), chitosan (CT) and a gold–chitosan (AuCT) hybrid to form 3-AuNPs, 3-CT and 3-AuCT, respectively. The conjugates afforded a decrease in fluorescence quantum yield with a corresponding increase in the triplet and singlet quantum yields compared to complex 3. The in vitro dark cytotoxicity and photodynamic therapy activity (PDT) of complex 3 and 3-AuCT composites were investigated against epithelial breast cancer cells (MCF-7) with both the samples showing minimum dark cytotoxicity. They both accounted for a cell viability of ≥90% at a concentration of ≤59.2 μg mL−1. 3-AuCT showed better PDT activity (compared to 3 alone) with less than 50% viable cells at a concentration of ≥29.6 μg mL−1 making it potentially applicable for PDT. On the other hand, AuCT displayed some activity against cancer cells, probably due to photothermal activity since gold is a light absorber, however it had more than 50% viable cells at a concentration of ≤59.2 μg mL−1.
- Full Text:
- Date Issued: 2018
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
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
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164841 , vital:41177 , DOI: 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.
- 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
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164841 , vital:41177 , DOI: 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.
- Full Text:
- Date Issued: 2014
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
A STAT3 of addiction: adipose tissue, adipocytokine signalling and STAT3 as mediators of metabolic remodelling in the tumour microenvironment
- Kadye, Rose, Stoffels, Mihlali, Fanucci, Sidne, Mbanxa, Siso, Prinsloo, Earl
- Authors: Kadye, Rose , Stoffels, Mihlali , Fanucci, Sidne , Mbanxa, Siso , Prinsloo, Earl
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149395 , vital:38846 , https://doi.org/10.3390/cells9041043
- Description: Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling. As a downstream effector of adipocytokines and cytokines, its canonical and non-canonical activities affect mitochondrial functioning and cancer metabolism. In this review, we examine the central role played by the crosstalk between the transcriptional and mitochondrial roles of STAT3 to promote survival and further oncogenesis within the tumour microenvironment with a particular focus on adipose-breast cancer interactions.
- Full Text:
- Date Issued: 2020
- Authors: Kadye, Rose , Stoffels, Mihlali , Fanucci, Sidne , Mbanxa, Siso , Prinsloo, Earl
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149395 , vital:38846 , https://doi.org/10.3390/cells9041043
- Description: Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling. As a downstream effector of adipocytokines and cytokines, its canonical and non-canonical activities affect mitochondrial functioning and cancer metabolism. In this review, we examine the central role played by the crosstalk between the transcriptional and mitochondrial roles of STAT3 to promote survival and further oncogenesis within the tumour microenvironment with a particular focus on adipose-breast cancer interactions.
- Full Text:
- Date Issued: 2020
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
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
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
Dynamic mitochondrial localisation of STAT3 in the cellular adipogenesis model 3T3-L1:
- Kramer, Adam H, Edkins, Adrienne L, Hoppe, Heinrich C, Prinsloo, Earl
- Authors: Kramer, Adam H , Edkins, Adrienne L , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164885 , vital:41181 , DOI: 10.1002/jcb.25076
- Description: A mechanistic relationship exists between protein localisation, activity and cellular differentiation. Understanding the contribution of these molecular mechanisms is required for elucidation of conditions that drive development. Literature suggests non‐canonical translocation of the Signal Transducer and Activator of Transcription 3 (STAT3) to the mitochondria contributes to the regulation of the electron transport chain, cellular respiration and reactive oxygen species production. Based on this we investigated the role of mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular differentiation using the well‐defined mouse adipogenic model 3T3-L1.
- Full Text:
- Date Issued: 2015
- Authors: Kramer, Adam H , Edkins, Adrienne L , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164885 , vital:41181 , DOI: 10.1002/jcb.25076
- Description: A mechanistic relationship exists between protein localisation, activity and cellular differentiation. Understanding the contribution of these molecular mechanisms is required for elucidation of conditions that drive development. Literature suggests non‐canonical translocation of the Signal Transducer and Activator of Transcription 3 (STAT3) to the mitochondria contributes to the regulation of the electron transport chain, cellular respiration and reactive oxygen species production. Based on this we investigated the role of mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular differentiation using the well‐defined mouse adipogenic model 3T3-L1.
- Full Text:
- Date Issued: 2015
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
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164830 , vital:41176 , DOI: 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
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164830 , vital:41176 , DOI: 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
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
Effects of pluronic silica nanoparticles on the photophysical and photodynamic therapy behavior of triphenyl-p-phenoxy benzoic acid metalloporphyrins
- Managa, Muthumuni, Britton, Jonathan, Prinsloo, Earl, Nyokong, Tebello
- Authors: Managa, Muthumuni , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/239698 , vital:50756 , xlink:href="https://doi.org/10.1080/00958972.2016.1236372"
- Description: 5, 10, 15, Triphenyl-20-p-phenoxy benzoic acid porphyrins (P) containing Zn (ZnP), Ga (GaP), and Si (SiP) were synthesized and conjugated to pluronic-silica (PluS) nanoparticles (NPs) where the fluorescence and singlet oxygen generating behavior of the porphyrins were investigated. The highest singlet oxygen quantum yield (ΦΔ) was obtained for ZnP. When the porphyrins were conjugated to the PluS NPs, the ΦΔ was quenched and fluorescence was enhanced. The pore size of the NPs upon conjugation decreased from 18.9 nm for PluS NPs to 2.4 nm (for ZnP as an example) as determined by applying the Brunauer–Emmett–Teller method. The porphyrin complexes and their conjugates were tested for their photodynamic therapy (PDT) activity on MCF-7 breast cancer cells. It was found that ZnP and its conjugate showed the highest PDT activity. The p > 0.05 indicated that ZnP is significantly different than GaP and SiP.
- Full Text:
- Date Issued: 2016
- Authors: Managa, Muthumuni , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/239698 , vital:50756 , xlink:href="https://doi.org/10.1080/00958972.2016.1236372"
- Description: 5, 10, 15, Triphenyl-20-p-phenoxy benzoic acid porphyrins (P) containing Zn (ZnP), Ga (GaP), and Si (SiP) were synthesized and conjugated to pluronic-silica (PluS) nanoparticles (NPs) where the fluorescence and singlet oxygen generating behavior of the porphyrins were investigated. The highest singlet oxygen quantum yield (ΦΔ) was obtained for ZnP. When the porphyrins were conjugated to the PluS NPs, the ΦΔ was quenched and fluorescence was enhanced. The pore size of the NPs upon conjugation decreased from 18.9 nm for PluS NPs to 2.4 nm (for ZnP as an example) as determined by applying the Brunauer–Emmett–Teller method. The porphyrin complexes and their conjugates were tested for their photodynamic therapy (PDT) activity on MCF-7 breast cancer cells. It was found that ZnP and its conjugate showed the highest PDT activity. The p > 0.05 indicated that ZnP is significantly different than GaP and SiP.
- Full Text:
- Date Issued: 2016
Synthesis and dark toxicity of 5-(4-carboxyphenyl)-10, 15, 20-tris (phenyl)-porphyrinato chlorido gallium (III) when conjugated to δ-aminolevulinic acid
- Managa, Muthumuni, Mkhize, Scebi, Britton, Jonathan, Prinsloo, Earl, Nyokong, Tebello
- Authors: Managa, Muthumuni , Mkhize, Scebi , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/240014 , vital:50789 , xlink:href="https://doi.org/10.1080/00958972.2016.1223292"
- Description: 5-(4-Carboxyphenyl)-10,15,20-tris(phenyl)-porphyrinato chlorido gallium(III) (2) was synthesized and then linked to ethyl ester δ-aminolevulinic acid to form 3. There was no shift in Soret band following conjugation. The fluorescence and singlet oxygen generating behavior of the porphyrins were also investigated. The highest singlet oxygen quantum yield (ΦΔ) obtained was that of 3. Complexes 2 and 3 as well as metal free 5-(4-carboxyphenyl)-10,15,20-tris(phenyl)-porphyrinato showed no dark toxicity on MCF-7 breast cancer cells.
- Full Text:
- Date Issued: 2016
- Authors: Managa, Muthumuni , Mkhize, Scebi , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/240014 , vital:50789 , xlink:href="https://doi.org/10.1080/00958972.2016.1223292"
- Description: 5-(4-Carboxyphenyl)-10,15,20-tris(phenyl)-porphyrinato chlorido gallium(III) (2) was synthesized and then linked to ethyl ester δ-aminolevulinic acid to form 3. There was no shift in Soret band following conjugation. The fluorescence and singlet oxygen generating behavior of the porphyrins were also investigated. The highest singlet oxygen quantum yield (ΦΔ) obtained was that of 3. Complexes 2 and 3 as well as metal free 5-(4-carboxyphenyl)-10,15,20-tris(phenyl)-porphyrinato showed no dark toxicity on MCF-7 breast cancer cells.
- Full Text:
- Date Issued: 2016
Effects of Pluronic F127 micelles as delivering agents on the vitro dark toxicity and photodynamic therapy activity of carboxy and pyrene substituted porphyrins
- Managa, Muthumuni, Britton, Jonathan, Prinsloo, Earl, Nyokong, Tebello
- Authors: Managa, Muthumuni , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/234439 , vital:50196 , xlink:href="https://doi.org/10.1016/j.poly.2018.06.031"
- Description: Metal free, Zn and ClGa containing carboxyphenoxy and phenoxy groups (complexes 1) and pyrene groups (complexes 2) were synthesized and embedded into Pluronic F127 micelles (represented as F127). Dark toxicity and photodynamic therapy activities of the embedded porphyrins were successfully studied on MCF-7 breast cancer cells. Dark toxicity showed more than 80% cell viability for all complexes. It was found that 1-Zn + F127 showed better photodynamic therapy activity compared to 1-H2 + F127, and 1-ClGa + F127, corresponding to the high partition coefficient for the Zn porphyrin derivatives. The same applies to 2-Zn + F127 compared to 2-H2 + F127, 2-ClGa + F127. 1-ClGa and 1-Zn were also linked to Pluronic F127 silica nanoparticles. PDT activities for embedded 1-ClGa + F127 and 1-Zn + F127 were much higher than when linked to Pluronic silica nanoparticles (PluS NPs), showing the importance of loading of porphyrins into Pluronic F127 as a drug delivering agent rather than linking. PDT studies at the highest concentration of 60 µg/ml showed decrease in cell viability down to 15.9% for 2-Zn + F127. The Kp was determined in biphasic octanol and water system.
- Full Text:
- Date Issued: 2018
- Authors: Managa, Muthumuni , Britton, Jonathan , Prinsloo, Earl , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/234439 , vital:50196 , xlink:href="https://doi.org/10.1016/j.poly.2018.06.031"
- Description: Metal free, Zn and ClGa containing carboxyphenoxy and phenoxy groups (complexes 1) and pyrene groups (complexes 2) were synthesized and embedded into Pluronic F127 micelles (represented as F127). Dark toxicity and photodynamic therapy activities of the embedded porphyrins were successfully studied on MCF-7 breast cancer cells. Dark toxicity showed more than 80% cell viability for all complexes. It was found that 1-Zn + F127 showed better photodynamic therapy activity compared to 1-H2 + F127, and 1-ClGa + F127, corresponding to the high partition coefficient for the Zn porphyrin derivatives. The same applies to 2-Zn + F127 compared to 2-H2 + F127, 2-ClGa + F127. 1-ClGa and 1-Zn were also linked to Pluronic F127 silica nanoparticles. PDT activities for embedded 1-ClGa + F127 and 1-Zn + F127 were much higher than when linked to Pluronic silica nanoparticles (PluS NPs), showing the importance of loading of porphyrins into Pluronic F127 as a drug delivering agent rather than linking. PDT studies at the highest concentration of 60 µg/ml showed decrease in cell viability down to 15.9% for 2-Zn + F127. The Kp was determined in biphasic octanol and water system.
- Full Text:
- Date Issued: 2018