Yuanyuan Wang, Tao Li, Hui Zhou, Chunyu Liu

Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

Correspondence: Chunyu Liu, Email 2608092067@qq.com

Abstract: Photodynamic therapy (PDT), as a non-invasive treatment modality, has shown potential as an alternative to traditional therapies in lung cancer treatment. However, its clinical application is still limited by key challenges, including low photosensitizer (PS) delivery efficiency, tumor microenvironment hypoxia, and the restricted diffusion of reactive oxygen species (ROS). This review systematically discusses innovative strategies employed by nanocarrier delivery systems to overcome these bottlenecks in PDT. The first section focuses on the application and challenges of PDT in lung cancer treatment: although PDT induces localized tumor cell death through ROS generation mediated by PSs, its efficacy is hindered by the delivery barriers of hydrophobic PSs to the lung, insufficient ROS generation due to tumor hypoxia, and PS self-quenching. The second section presents nanotechnology-driven solutions: 1) using nanocarriers equipped with catalase or hemoglobin and perfluorocarbon to alleviate tumor hypoxia and enhance ROS production; 2) modifying the surface of nanocarriers with targeting ligands to improve PS accumulation in tumor tissues and reduce self-quenching effects; and 3) combining PS-loaded nanocarriers with immune checkpoint inhibitors and chemotherapy agents to synergistically enhance anti-tumor efficacy and suppress metastasis. Future research should focus on further optimizing the biocompatibility, clinical translation potential, and multimodal synergistic mechanisms of nanocarriers, to promote the widespread application of PDT in precise lung cancer treatment.

Keywords: lung cancer treatment, nanocarrier delivery systems, photodynamic therapy, photosensitizers, fighting hypoxia