Photodynamic Therapy of Aluminum Phthalocyanine Tetra Sodium 2-Mercaptoacetate Linked to PEGylated Copper-Gold Bimetallic Nanoparticles on Colon Cancer Cells.

This work reports for the first time on the synthesis, characterization, and photodynamic therapy efficacy of the novel aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (AlClPcTS41) when alone and when conjugated to PEGylated copper-gold bimetallic nanoparticles (PEG-CuAuNPs) as photosensitizers on colon cancer cells (Caco-2). The novel AlClPcTS41 was covalently linked to the PEG-CuAuNPs via an amide bond to form AlClPcTS41-PEG-CuAuNPs. The amide bond was successfully confirmed using FTIR while the crystal structures were studied using XRD. The morphological and size variations of the PEG-CuAuNPs and AlClPcTS41-PEG-CuAuNPs were studied using TEM, while the hydrodynamic sizes and polydispersity of the particles were confirmed using DLS. The ground state electron absorption spectra were also studied and confirmed the typical absorption of metallated phthalocyanines and their nanoparticle conjugates. Subsequently, the subcellular uptake, cellular proliferation, and PDT anti-tumor effect of AlClPcTS41, PEG-CuAuNPs, and AlClPcTS41-PEG-CuAuNPs were investigated within in vitro Caco-2 cells. The designed AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs demonstrated significant ROS generation abilities that led to the PDT effect with a significantly decreased viable cell population after PDT treatment. These results demonstrate that the novel AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs had remarkable PDT effects against Caco-2 cells and may trigger apoptosis cell death pathway, indicating the potential of the AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs in enhancing the cytotoxic effect of PDT treatment.

Photodynamic Therapy Efficacy of Novel Zinc Phthalocyanine Tetra Sodium 2-Mercaptoacetate Combined with Cannabidiol on Metastatic Melanoma.

This work reports for the first time on the synthesis, characterization, and photodynamic therapy effect of a novel water-soluble zinc (II) 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (ZnPcTS41), on metastatic melanoma cells (A375) combined with cannabidiol (CBD). The ZnPcTS41 structure was confirmed using FTIR, NMR, MS, and elemental analysis while the electronic absorption spectrum was studied using UV-VIS. The study reports further on the dose-dependent effects of ZnPcTS41 (1-8 µM) and CBD alone (0.3-1.1 µM) at 636 nm with 10 J/cm2 on cellular morphology and viability. The IC50 concentrations of ZnPcTS41 and CBD were found to be 5.3 µM and 0.63 µM, respectively. The cytotoxicity effects of the ZnPcTS41 enhanced with CBD on A375 cells were assessed using MTT cell viability assay, ATP cellular proliferation and inverted light microscopy. Cell death induction was also determined via Annexin V-FITC-PI. The combination of CBD- and ZnPcTS41-mediated PDT resulted in a significant reduction in cell viability (15%***) and an increase in the late apoptotic cell population (25%*). These findings suggest that enhancing PDT with anticancer agents such as CBD could possibly obliterate cancer cells and inhibit tumor recurrence.

Nanoscale metal-organic frameworks as photosensitizers and nanocarriers in photodynamic therapy.

Photodynamic therapy (PDT) is a new therapeutic system for cancer treatment that is less invasive and offers greater selectivity than chemotherapy, surgery, and radiation therapy. PDT employs irradiation light of known wavelength to excite a photosensitizer (PS) agent that undergoes photochemical reactions to release cytotoxic reactive oxygen species (ROS) that could trigger apoptosis or necrosis-induced cell death in tumor tissue. Nanoscale metal-organic frameworks (NMOFs) have unique structural advantages such as high porosity, large surface area, and tunable compositions that have attracted attention toward their use as photosensitizers or nanocarriers in PDT. They can be tailored for specific drug loading, targeting and release, hypoxia resistance, and with photoactive properties for efficient response to optical stimuli that enhance the efficacy of PDT. In this review, an overview of the basic chemistry of NMOFs, their design and use as photosensitizers in PDT, and as nanocarriers in synergistic therapies is presented. The review also discusses the morphology and size of NMOFs and their ability to improve photosensitizing properties and localize within a targeted tissue for effective and selective cancer cell death over healthy cells. Furthermore, targeting strategies that improve the overall PDT efficacy through stimulus-activated release and sub-cellular internalization are outlined with relevance to in vitro and in vivo studies from recent years.

Hybrid Inorganic-Organic Core-Shell Nanodrug Systems in Targeted Photodynamic Therapy of Cancer.

Hybrid inorganic-organic core-shell nanoparticles (CSNPs) are an emerging paradigm of nanodrug carriers in the targeted photodynamic therapy (TPDT) of cancer. Typically, metallic cores and organic polymer shells are used due to their submicron sizes and high surface to volume ratio of the metallic nanoparticles (NPs), combined with enhances solubility, stability, and absorption sites of the organic polymer shell. As such, the high loading capacity of therapeutic agents such as cancer specific ligands and photosensitizer (PS) agents is achieved with desired colloidal stability, drug circulation, and subcellular localization of the PS agents at the cancer site. This review highlights the synthesis methods, characterization techniques, and applications of hybrid inorganic-organic CSNPs as loading platforms of therapeutic agents for use in TPDT. In addition, cell death pathways and the mechanisms of action that hybrid inorganic-organic core-shell nanodrug systems follow in TPDT are also reviewed. Nanodrug systems with cancer specific properties are able to localize within the solid tumor through the enhanced permeability effect (EPR) and bind with affinity to receptors on the cancer cell surfaces, thus improving the efficacy of short-lived cytotoxic singlet oxygen. This ability by nanodrug systems together with their mechanism of action during cell death forms the core basis of this review and will be discussed with an overview of successful strategies that have been reported in the literature.

Effect of symmetry and metal nanoparticles on the photophysicochemical and photodynamic therapy properties of cinnamic acid zinc phthalocyanine.

In this study, a novel asymmetric cinnamic acid zinc phthalocyanine (ZnPc, 1) containing three tert-butyl substituents is reported. The asymmetric ZnPc (1) is further linked to amino functionalized magnetic nanoparticles (AMNPs) (1-AMNPs) and to cysteine functionalized silver nanoparticles (cys-AgNPs) (1-cys-AgNPs) through an amide bond. 1-AMNPs and 1-cys-AgNPs improved the triplet and singlet oxygen quantum yields of complex 1, this was also observed with the previously reported 2-AMNPs when compared to 2 while 3-AMNPs yielded an unexpected decrease in triplet quantum yield as compared to 3. The silver nanoparticles (1-cys-AgNPs) had a better effect on improving the singlet oxygen quantum yield of complex 1 than the magnetic nanoparticles (1-AMNPs). The Pcs and conjugates recorded low cell cytotoxicity in the dark and high photocytotoxicity against MCF-7 cells in-vitro. MCF-7 cell viabilities of less than 50% were recorded at 80 µg/mL making the Pcs and conjugates under study potential candidates for use as photosensitizers in cancer therapy.

Photodynamic therapy activity of zinc phthalocyanine linked to folic acid and magnetic nanoparticles.

In this work, the photodynamic therapy (PDT) activities (using human carcinoma adherent MCF-7 cells) of zinc phthalocyanine derivatives: complexes 1 (Zn mono cinnamic acid phthalocyanine) and 2 (zinc mono carboxyphenoxy phthalocyanine) when covalently linked to folic acid (FA) and amine functionalized magnetic nanoparticles (AMNPs) are reported. The covalent linkage of asymmetric zinc cinnamic acid Pc (1) to FA (1-FA) through an amide bond is reported for the first time. Complex 1 is insoluble in water, but upon linkage to FA, (to form 1-FA) the molecule become water soluble, hence the UV-Vis spectrum and singlet oxygen quantum yield for 1-FA were also done in water since water solubility is essential for biological applications. The reported 2-FA is also water soluble. Linking complexes 1 and 2 to FA and AMNPs decreased the dark toxicity of 1 and 2 on MCF-7 cells. Pc-FA (1-FA and 2-FA) conjugates had better singlet oxygen quantum yields (Φ∆) in DMSO as compared to Pc-AMNPs (1-AMNPs and 2-AMNPs). The water- soluble 1-FA and 2-FA also achieved a better photodynamic therapy (PDT) activity as compared to 1-AMNPs and 2-AMNPs. Folic acid targeting on the tumor cells may have also facilitated better bioavailability of 1-FA and 2-FA and improved PDT activity on MCF-7 cells over AMNPs carriers.