Cell-penetrating peptide functionalized ZIF-90 platform for photodynamic-chemical combined therapy in colorectal cancer

Colorectal cancer (CRC) is one of the major concerns of developed nations. The combination of different treatment modalities has been shown to be effective in improving tumor therapy efficiency and reducing side effects. However, the synergistic anti-tumor efficiency and highly responsive drug release still remain challenging. Curcumin (CCM) has a chemotherapeutic effect as well as significant photodynamic activity, which is a promising component for the treatment of tumors. Herein, we report a cell-penetrating peptide functionalized ZIF-90-based drug delivery platform (PEG-CPP2@NPs) for synergistic photodynamic-chemical combined therapy in colorectal cancer. Polyethylene glycol (PEG)-conjugated CPP2 coating obviously increased the uptake of nanoparticles in tumor cells and their accumulation in tumor tissues. We conducted in vivo and in vitro experiments to evaluate the anti-tumor effects of CCM-loaded multifunctional nanoparticles. The PEG-CPP2@NPs exhibited significant tumor inhibition. After laser irradiation treatment, the generation of reactive oxygen species (ROS), mitochondrial damage, and cell apoptosis, as well as the expressions of Bax/Bcl-2, cytochrome C, and caspase-3, were all significantly enhanced. The tumor suppression rates in mice across the treatment groups were 25.46% for CCM, 33.16% for NPs, 43.5% for CCM+L, 48.45% for NPs+L, 66.05% for PEG-CPP2@NPs, and 80.64% for PEG-CPP2@NPs+L. This indicates that the functionalized ZIF-90 platform, when combined with chemotherapy and photodynamic therapy, has a stronger anti-tumor effect. Overall, the novel drug-delivery platform designed herein has demonstrated significant potential in the treatment of colon cancer and has provided a new approach for enhancing anti-tumor efficacy.