The development of ionic zinc(II) phthalocyanines for sono-photodynamic combination therapy of cervical and breast cancer
- Authors: Nene, Lindokuhle Cindy
- Date: 2023-03-31
- Subjects: Phthalocyanines , Sonochemistry , Photochemotherapy , Cancer Treatment
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422565 , vital:71958 , DOI 10.21504/10962/422565
- Description: This study focuses on the development of the sono-photodynamic combination therapy (SPDT) activity of phthalocyanines (Pcs) on the cervical and breast cancer cell lines in vitro. The SPDT technique utilizes ultrasound in combination with light to elicit cytotoxic effects for cancer eradication. In this work, a selection of tetra-peripherally substituted Zn(II) cationic and zwitterionic Pcs were prepared. The photophysical parameters of the Pcs were determined including their fluorescence behaviours and efficiency of the triplet excited state population. The effects of the ultrasonic parameters (frequencies (MHz) and power (W.cm-2)) on the stability of the Pcs were evaluated. Four parameters were evaluated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). The stability of the Pcs reduced with the increase in the ultrasonic power (for Par II and Par IV). The Par I showed the least degradation compared to the other parameters and was therefore used for the SPDT treatments. The sonodynamic (SDT), photodynamic (PDT) therapy activities of the Pcs were studied and compared to their SPDT efficacies. The Pcs showed reactive oxygen species generation during the SDT, PDT and SPDT treatments. For the SDT and SPDT, singlet oxygen (1O2) and hydroxyl radicals (•OH) were detected. For PDT, only the 1O2 were detected. The cell cytotoxicity studies for the Pcs showed relatively higher therapeutic efficacies for the SDT treatments compared to the PDT treatments, where the SPDT showed higher therapeutic efficacies compared to both the SDT and PDT monotreatments on both the cell lines in vitro. Overall, the combination treatments were better compared to the monotreatments. The activities of the Pcs were compared by their differences in structures, including the type of R-group, type of quaternizing agent and type of nanoparticle conjugates. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-31
- Authors: Nene, Lindokuhle Cindy
- Date: 2023-03-31
- Subjects: Phthalocyanines , Sonochemistry , Photochemotherapy , Cancer Treatment
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422565 , vital:71958 , DOI 10.21504/10962/422565
- Description: This study focuses on the development of the sono-photodynamic combination therapy (SPDT) activity of phthalocyanines (Pcs) on the cervical and breast cancer cell lines in vitro. The SPDT technique utilizes ultrasound in combination with light to elicit cytotoxic effects for cancer eradication. In this work, a selection of tetra-peripherally substituted Zn(II) cationic and zwitterionic Pcs were prepared. The photophysical parameters of the Pcs were determined including their fluorescence behaviours and efficiency of the triplet excited state population. The effects of the ultrasonic parameters (frequencies (MHz) and power (W.cm-2)) on the stability of the Pcs were evaluated. Four parameters were evaluated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). The stability of the Pcs reduced with the increase in the ultrasonic power (for Par II and Par IV). The Par I showed the least degradation compared to the other parameters and was therefore used for the SPDT treatments. The sonodynamic (SDT), photodynamic (PDT) therapy activities of the Pcs were studied and compared to their SPDT efficacies. The Pcs showed reactive oxygen species generation during the SDT, PDT and SPDT treatments. For the SDT and SPDT, singlet oxygen (1O2) and hydroxyl radicals (•OH) were detected. For PDT, only the 1O2 were detected. The cell cytotoxicity studies for the Pcs showed relatively higher therapeutic efficacies for the SDT treatments compared to the PDT treatments, where the SPDT showed higher therapeutic efficacies compared to both the SDT and PDT monotreatments on both the cell lines in vitro. Overall, the combination treatments were better compared to the monotreatments. The activities of the Pcs were compared by their differences in structures, including the type of R-group, type of quaternizing agent and type of nanoparticle conjugates. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-31
Enhanced mitochondria destruction on MCF-7 and HeLa cell lines in vitro using triphenyl-phosphonium-labelled phthalocyanines in ultrasound-assisted photodynamic therapy activity
- Nene, Lindokuhle Cindy, Magadla, Aviwe, Nyokong, Tebello
- Authors: Nene, Lindokuhle Cindy , Magadla, Aviwe , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/295766 , vital:57376 , xlink:href="https://doi.org/10.1016/j.jphotobiol.2022.112553"
- Description: This work reports on the reactive oxygen species (ROS) generation and the therapeutic activities of new triphenyl-phosphonium-labelled phthalocyanines (Pcs), the 2,9,16,23-tetrakis(N-(N-butyl-4-triphenyl-phosphonium)- pyridine-4-yloxy) Zn(II) Pc (3) and 2,9,16,23-tetrakis-(N-(N-butyl-4-triphenyl-phosphonium)-morpholino) Zn(II) Pc (4) upon exposure to light, ultrasound and the combination of light and ultrasound. Two types of ROS were detected: the singlet oxygen (1O2) and hydroxyl radicals. For light irradiations, only the 1O2 was detected. An increase in the ROS generation was observed for samples treated with the combination of light and ultrasound compared to the light and ultrasound mono-treatments. The in vitro anticancer activity through photodynamic (PDT) and sonodynamic (SDT) therapy for the Pcs were also determined and compared to the photo-sonodynamic combination therapy (PSDT). The two cancer cell lines used for the in vitro studies included the Michigan Cancer Foundation-7 (MCF-7) breast cancer and Henrietta Lacks (HeLa) cervical cancer cell lines. The SDT treatments showed improved therapeutic efficacy on the cancer cells for both the Pcs compared to PDT. PSDT showed better therapeutic efficacy compared to both the PDT and SDT mono-treatments.
- Full Text:
- Date Issued: 2022
- Authors: Nene, Lindokuhle Cindy , Magadla, Aviwe , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/295766 , vital:57376 , xlink:href="https://doi.org/10.1016/j.jphotobiol.2022.112553"
- Description: This work reports on the reactive oxygen species (ROS) generation and the therapeutic activities of new triphenyl-phosphonium-labelled phthalocyanines (Pcs), the 2,9,16,23-tetrakis(N-(N-butyl-4-triphenyl-phosphonium)- pyridine-4-yloxy) Zn(II) Pc (3) and 2,9,16,23-tetrakis-(N-(N-butyl-4-triphenyl-phosphonium)-morpholino) Zn(II) Pc (4) upon exposure to light, ultrasound and the combination of light and ultrasound. Two types of ROS were detected: the singlet oxygen (1O2) and hydroxyl radicals. For light irradiations, only the 1O2 was detected. An increase in the ROS generation was observed for samples treated with the combination of light and ultrasound compared to the light and ultrasound mono-treatments. The in vitro anticancer activity through photodynamic (PDT) and sonodynamic (SDT) therapy for the Pcs were also determined and compared to the photo-sonodynamic combination therapy (PSDT). The two cancer cell lines used for the in vitro studies included the Michigan Cancer Foundation-7 (MCF-7) breast cancer and Henrietta Lacks (HeLa) cervical cancer cell lines. The SDT treatments showed improved therapeutic efficacy on the cancer cells for both the Pcs compared to PDT. PSDT showed better therapeutic efficacy compared to both the PDT and SDT mono-treatments.
- Full Text:
- Date Issued: 2022
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
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