Phototherapy in cancer treatment: strategies and challenges

作者：Yeyu Cai, Tian Chai, William Nguyen, Jiayi Liu, Enhua Xiao, Xin Ran, Yuping Ran, Dan Du, Wei Chen, Xiangyu Chen · 发表于：Signal Transduction and Targeted Therapy · 年份：2025 · DOI：10.1038/s41392-025-02140-y · 被引用次数：343 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Cancer, Hypoxia, and Metabolism

Phototherapy has emerged as a promising modality in cancer treatment, garnering considerable attention for its minimal side effects, exceptional spatial selectivity, and optimal preservation of normal tissue function. This innovative approach primarily encompasses three distinct paradigms: Photodynamic Therapy (PDT), Photothermal Therapy (PTT), and Photoimmunotherapy (PIT). Each of these modalities exerts its antitumor effects through unique mechanisms-specifically, the generation of reactive oxygen species (ROS), heat, and immune responses, respectively. However, significant challenges impede the advancement and clinical application of phototherapy. These include inadequate ROS production rates, subpar photothermal conversion efficiency, difficulties in tumor targeting, and unfavorable physicochemical properties inherent to traditional phototherapeutic agents (PTs). Additionally, the hypoxic microenvironment typical of tumors complicates therapeutic efficacy due to limited agent penetration in deep-seated lesions. To address these limitations, ongoing research is fervently exploring innovative solutions. The unique advantages offered by nano-PTs and nanocarrier systems aim to enhance traditional approaches' effectiveness. Strategies such as generating oxygen in situ within tumors or inhibiting mitochondrial respiration while targeting the HIF-1α pathway may alleviate tumor hypoxia. Moreover, utilizing self-luminescent materials, near-infrared excitation sources, non-photoact...