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:
- 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.
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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:
- 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.
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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:
- 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.
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