Nanoparticle-mediated delivery systems in photodynamic therapy of colorectal cancer

Colorectal cancer (CRC) involving a malignant tumour remains one of the greatest con-tributing causes of fatal mortality and has become the third globally ranked malignancy in terms of cancer-associated deaths. Conventional CRC treatment approaches such as surgery, radiation, and chemotherapy are the most utilized approaches to treat this disease. However, they are limited by low selectivity and systemic toxicity, so they cannot completely eradicate this disease. Photodynamic therapy (PDT) is an emerging therapeutic modality that exerts selective cytotoxicity to cancerous cells through the activation of photosensitizers (PSs) under light irradiation to produce cytotoxic reactive oxygen species (ROS), which then cause cancer cell death. Cumulative research findings have highlighted the significant role of traditional PDT in CRC treatment; however, the therapeutic efficacy of the classical PDT strategy is restricted due to skin photosensitivity, poor cancerous tissue specificity, and limited penetration of light. The application of nanoparticles in PDT can mitigate some of these shortcomings and enhance the targeting ability of PS in order to effectively use PDT against CRC as well as to reduce systemic side effects. Although 2D culture models are widely used in cancer research, they have some limitations. Therefore, 3D models in CRC PDT, particularly multicellular tumour spheroids (MCTS), have attracted researchers. This review summarizes several photosensitizers that are currently used in CRC PDT and gives an overview of recent advances in nanoparticle application for enhanced CRC PDT. In addition, the progress of 3D-model applications in CRC PDT is discussed.