Anticancer photodynamic activities of triphenylphosphine-labelled phthalocyanines and their bovine serum albumin-gold nanoparticles- complexes on melanoma A375 cell lines in vitro.

This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (1O2) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.

Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer.

Cancer remains one of the diseases with the highest incidence and mortality globally. Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness, non-controllability, and development of resistance for some, including chemotherapy, radiation, and surgery. Sono-photodynamic combinatorial therapy (SPDT) has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic approach. SPDT combines the mechanism of action of sonodynamic therapy (SDT), which uses ultrasound, and photodynamic therapy (PDT), which uses light, to activate a sensitizer and initiate cancer eradication. The use of phthalocyanines (Pcs) as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and PDT. This review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.

Phthalocyanine-based probes in alleviating or evading tumour-hypoxia for enhanced photo- and/ sono-mediated therapeutic efficacies.

This review discusses the possible methods for improving therapeutic efficacies of phthalocyanine (Pcs) -based therapeutic probes in photo- and sono-dynamic therapies under hypoxic conditions. Herein, the structural design strategies including varying the central metal, position substituents and the effects of adjuvant used in supplementing the therapeutics activities of Pcs or formation of NPs are discussed for cancer therapies in hypoxic conditions. Different mechanisms induced for cell death influenced by the compositions of the Pcs-probes are discussed. The focus mainly highlights the oxygen (O2) -dependent mechanisms including methods of supplementing tumour microenvironment O2-concentrations to promote PDT or SDT therapies. Alternatively, O2-independent mechanisms mainly used to evade hypoxia by stimulating anticancer processes that don't require O2 to initiate cell death, such as the Fenton reaction or thermal ablation effects.

The in-vitro proliferation-suppression of MCF-7 and HeLa cell lines mediated by differently substituted ionic phthalocyanines in sonodynamic therapy supplemented-photodynamic therapy.

This work focuses on the study of the effects of the ultrasonic frequency (MHz) and power (W.cm-2) on the stability, reactive oxygen species yields and cytotoxicity activities of differently substituted ionic phthalocyanines (Pcs) in sonodynamic therapy (SDT). Four ultrasonic parameters were investigated: 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). A higher degradation of the Pcs was observed with increasing power at the Par II. Two reactive oxygen species (ROS) were detected in the ultrasound treated Pcs: singlet oxygen and hydroxyl radicals. Due to minimal degradation of most Pcs, Par I was chosen for SDT, photodynamic therapy (PDT), and photo-sonodynamic therapy (PSDT) against Michigan Cancer Foundation-7 and Henrietta Lacks cancer cell lines. PSDT generally showed improved therapeutic efficacies of the Pcs compared to the SDT and PDT mono treatments.

Enhanced mitochondria destruction on MCF-7 and HeLa cell lines in vitro using triphenyl-phosphonium-labelled phthalocyanines in ultrasound-assisted photodynamic therapy activity.

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.

Photo-sonodynamic combination activity of cationic morpholino-phthalocyanines conjugated to nitrogen and nitrogen-sulfur doped graphene quantum dots against MCF-7 breast cancer cell line in vitro.

In this work, we explore the reactive oxygen species (ROS) generation abilities of cationic morpholino-substituted-phthalocyanine (Pc) conjugated to nitrogen (NGQDs) and nitrogen-sulfur (NSGQDs) doped-graphene quantum dots upon irradiation with light for photodynamic therapy (PDT), ultrasound for sonodynamic therapy (SDT) and the combination of both in photo-sonodynamic therapy (PSDT). The in vitro cytotoxicity studies were conducted using the Michigan Cancer Foundation-7 breast cancer cell lines (MCF-7 cells). For PDT treatments, only the 1O2 was detected for all the sensitizers, whereas both the 1O2 and •OH radicals were evident after SDT and PSDT treatments. An increase in the 1O2 generation was observed for the conjugates compared to the GQDs and the Pc alone. However, the •OH radicals were reduced in the conjugates compared to the GQDs and the Pc alone. The NGQDs generally showed better ROS generation efficacy compared to the NSGQDs, alone and in the conjugates. The combination therapy also shows improved efficacy compared to the monotherapies for the Pcs and Pc-GQDs conjugates.

Effect of ultrasonic frequency and power on the sonodynamic therapy activity of cationic Zn(II) phthalocyanines.

We report on the sonodynamic activity of cationic phthalocyanines (Pcs) and the effect of the variation of two parameters: ultrasound frequency and power (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)) on the efficiency of their reactive oxygen species generation and cancer eradication in vitro thereof. Where Par stands for the various combinations of these parameters. Four Pcs were investigated with substituents bearing diethylamine, ortho- and para-pyridine and morpholine groups. Overall, the para-pyridine and morpholine Pcs showed substantial sono-activity in the various ultrasound parameters with Par I and IV generally showing better singlet oxygen and hydroxyl radicals generation confirmed by electron paramagnetic resonance spectroscopy. In some cases, very high hydroxyl radicals' generation was observed at Par II. Furthermore, the fragmentation of the Pcs after Par II treatments was confirmed using UV-vis and magnetic circular dichroism spectroscopy. The reactive species generation efficacy decreased at Par III for all samples. Ultrasound assisted cytotoxicity of the Pcs was confirmed in vitro using the human (Michigan Cancer Foundation-7) breast cancer cell line.