Zinc Phthalocyanine Tetrasulfonate-Loaded Ag@mSiO2 Nanoparticles for Active Targeted Photodynamic Therapy of Colorectal Cancer

Abstract

Colorectal cancer has high morbidity and mortality rate, with a high level of metastasis and recurrence due to the poor therapeutic effects. Photodynamic therapy (PDT) as an emerging clinical modality for cancer treatment provides remarkable advantages over existing treatments by generating reactive oxygen species (ROS) through light irradiating photosensitizers (PSs) in the presence of oxygen. PDT can induce immunity against recurrence and destruction of metastases. The application of nanoparticles (NPs) in targeted cancer therapy is coming to light to circumvent the limitations associated with low physiological solubility and lack of selectivity of the PS towards tumor sites. In this in vitro study, we proved the added value of NP systems on PS efficacy and a tumor-targeting ligand. Using core/shell Ag@mSiO2 NPs loaded with ZnPcS4 PS and folic acid (FA), stronger cellular localization in the human colorectal cancer cell line (Caco-2) was observed compared to the passive NC and free PS. Additionally, light-induced photodynamic activation of the ZnPcS4/Ag@mSiO2-FA nanoconjugate (NC) elicited a strong cytotoxicity effect mediated by post-PDT. The results also revealed that the active NC was able to decrease the cell viability remarkably to 38.0% ± 4.2 *** compared to the passive NC (67.0% ± 7.4*) under 0.125 µM ZnPcS4 (IC50). More importantly, the actively targeted NC-induced apoptosis where cell cycle analysis elaborated on cell death through the G0 phase, indicating the final NC’s efficacy 20 hr post-PDT treatment.

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

“…In the past decade, CRC incidence rate has been on the rise, and in just the year 2020, CRC incidence rate was estimated to have accounted for approximately 10% of global cancer incidence [1]. Several common CRC treatment modalities include invasive surgery, chemotherapy, and radiotherapy [2]. Nevertheless, these therapeutic modalities still lack a complete cure for CRC due to their shortcomings such as invasiveness, undesirable systemic side effects, and toxicity [2].…”

“…Several common CRC treatment modalities include invasive surgery, chemotherapy, and radiotherapy [2]. Nevertheless, these therapeutic modalities still lack a complete cure for CRC due to their shortcomings such as invasiveness, undesirable systemic side effects, and toxicity [2]. Accordingly, there is an unmet need to obtain more improved and effective therapeutic outcomes for CRC, and potentially reduce side effects; thus, an urgent need for the development of prospective CRC treatment is required [2].…”

“…Nevertheless, these therapeutic modalities still lack a complete cure for CRC due to their shortcomings such as invasiveness, undesirable systemic side effects, and toxicity [2]. Accordingly, there is an unmet need to obtain more improved and effective therapeutic outcomes for CRC, and potentially reduce side effects; thus, an urgent need for the development of prospective CRC treatment is required [2]. Photodynamic therapy (PDT) is a developing antitumor approach that is less harmful to patients, selectively eradicates cancerous cells with minimal side effects, and is tolerable to repeated doses with far more effectiveness as compared to the conventional CRC treatment [3].…”

Cytotoxic Effects of Combinative ZnPcS4 Photosensitizer Photodynamic Therapy (PDT) and Cannabidiol (CBD) on a Cervical Cancer Cell Line

“…Zinc phthalocyanine tetrasulfonate (ZnPcS 4 ) has been designed as an amphiphilic PS agent to promote uptake, as well as circumvent any issues associated with solubility and aggregation [ 16 ]. Studies by Pashkovskaya et al (2007) and Montaseri et al (2022) noted that Pc complexes, such as anionic ZnPcS 4 PSs, can efficiently bind to cancer tumor phospholipid membranes, through metal–phosphate coordination [ 16 , 17 ].…”

“…Zinc phthalocyanine tetrasulfonate (ZnPcS 4 ) has been designed as an amphiphilic PS agent to promote uptake, as well as circumvent any issues associated with solubility and aggregation [ 16 ]. Studies by Pashkovskaya et al (2007) and Montaseri et al (2022) noted that Pc complexes, such as anionic ZnPcS 4 PSs, can efficiently bind to cancer tumor phospholipid membranes, through metal–phosphate coordination [ 16 , 17 ]. Therefore, ZnPcS 4 PSs can spontaneously accumulate in tumors through an enhanced permeability and retention (EPR) effect, due to the binding of its tetrasulfonated groups to cancer cell membranes (which have high phospholipid contents), and so allow for passively selective accumulation [ 16 , 17 , 18 , 19 ].…”