Temoporfin loaded g-C₃N₄/CuO nanocarrier for treatment of hypoxic tumors by synergistic chemo-photodynamic therapy

A multifunctional nanocarrier is prepared by loading photosensitizer drug Temoporfin on g-C₃N₄/CuO (GC) nanocomposites. g-C₃N₄/CuO formulation functionalized with folic acid exhibited the drug encapsulation efficiency (%) of 87.8±0.52 %. At pH 5.4, 53.79±0.18% and 75.50±1.25% drug was released from the nanocarrier in the absence and presence of NIR light, respectively. Cytotoxic effects of temoporfin, GC NC, and FA-GC/Tem are studied against human breast cancer (MDA-MB-231) and lung cancer (A549) cell line for 48 h, in a dose-dependent manner. At the concentration of 2.50 mg/mL, g-C₃N₄/CuO nanocomposite treated MDA-MB-231 showed cell viability of 6.99% and 15.96% with and without NIR irradiation, respectively. Whereas, Tem loaded FA-GC, the cell viability was observed to be 2.48% and 18.09% respectively. The IC₅₀ values of Tem, GC, and Tem-loaded FA-GC are 0.46, 5.13, and 118.95 μg/mL in the presence of NIR light. Besides, IC₅₀ without NIR exposure are found to be 4.90, 44.6, and 594.28 μg/mL, respectively. Lung cancer (A549) cell line treated with 2.5 mg/mL concentration of GC and Tem loaded FA-GC showed 3.18 % and 10.40% cell viability. The biocompatibility of the Tem-loaded FA-GC towards the immortalized human keratinocyte (HaCaT) Cell line is also confirmed. In silico experiments are carried out to study the interaction between g-C₃N₄/CuO with cancer proliferation proteins like EGFR (Kinase inhibitors), HCA (Human Carbonic Anhydrase), and Akt1 (Protein kinase B). The diphenylisobenzofuran (DPBF) assay and Terephthalic acid assay proved the generation of singlet oxygen and OH* radicals respectively, which play an important role in anticancer activity.