Cai Yeyu, Chai Tian, Nguyen William, Liu Jiayi, Xiao Enhua, Ran Xin, Ran Yuping, Du Dan, Chen Wei, Chen Xiangyu
Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), Xi'an, Shanxi Province, China.
Signal Transduct Target Ther. 2025 Apr 2;10(1):115. doi: 10.1038/s41392-025-02140-y.
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-photoactivated sensitizers, and wireless light delivery systems can improve light penetration. Furthermore, integrating immunoadjuvants and modulating immunosuppressive cell populations while deploying immune checkpoint inhibitors holds promise for enhancing immunogenic cell death through PIT. This review seeks to elucidate the fundamental principles and biological implications of phototherapy while discussing dominant mechanisms and advanced strategies designed to overcome existing challenges-ultimately illuminating pathways for future research aimed at amplifying this intervention's therapeutic efficacy.
光疗法已成为癌症治疗中一种很有前景的治疗方式，因其副作用极小、空间选择性卓越以及能最佳地保留正常组织功能而备受关注。这种创新方法主要包括三种不同的模式：光动力疗法（PDT）、光热疗法（PTT）和光免疫疗法（PIT）。这些模式中的每一种都通过独特的机制发挥其抗肿瘤作用，具体而言，分别是产生活性氧（ROS）、热和免疫反应。然而，重大挑战阻碍了光疗法的进展和临床应用。这些挑战包括ROS产生率不足、光热转换效率欠佳、肿瘤靶向困难以及传统光治疗剂（PTs）固有的不良物理化学性质。此外，肿瘤典型的缺氧微环境由于深层病变中药物渗透受限而使治疗效果复杂化。为解决这些局限性，正在进行的研究正在热切探索创新解决方案。纳米PTs和纳米载体系统提供的独特优势旨在提高传统方法的有效性。诸如在肿瘤内原位产生氧气或在靶向缺氧诱导因子-1α（HIF-1α）途径的同时抑制线粒体呼吸等策略可能会缓解肿瘤缺氧。此外，利用自发光材料、近红外激发源、非光活化敏化剂和无线光输送系统可以改善光穿透。此外，在部署免疫检查点抑制剂的同时整合免疫佐剂并调节免疫抑制细胞群体有望通过PIT增强免疫原性细胞死亡。这篇综述旨在阐明光疗法的基本原理和生物学意义，同时讨论旨在克服现有挑战的主要机制和先进策略，最终为旨在提高这种干预治疗效果的未来研究指明方向。
