Strategies to enhance the effects of nanotechnology-mediated photodynamic therapy

Photodynamic therapy (PDT) is a noninvasive therapeutic approach, particularly effective in tumor treatment. PDT utilizes photosensitizers (PSs) to absorb light at specific wavelengths, converting photon energy into chemical energy and subsequently generating cytotoxic reactive oxygen species (ROS). These ROS trigger cell death through apoptosis, necrosis and autophagy-related pathways. Compared with conventional therapies, PDT exhibits significant advantages, including high selectivity, repeatability, enhanced safety, minimal side effects, low drug resistance, and compatibility with radiotherapy or chemotherapy. However, due to the limited tissue penetration depth of light, PDT demonstrates suboptimal efficacy in treating deep tumors. Additionally, limitations such as poor targeting of photosensitizers and unfavorable factors in the tumor microenvironment greatly restrict PDT's therapeutic efficacy and clinical applicability. To enhance PDT efficacy, various strategies have been explored, among which nanotechnology has emerged as a key research focus. This review summarizes multiple approaches to augmenting nanotechnology-mediated PDT, with emphasis on achieving targeted delivery of photosensitizers (tissue, cell, and organelle-level), improving the performance of photosensitizers and modulating the tumor microenvironment. These insights provide theoretical guidance and practical references for developing novel and efficient PDT nanoplatforms. We conducted the literature search in PubMed, Elsevier ScienceDirect, Web of Science, Wiley and Scopus (from 2004 to 2025).