Zou Jinglin, Jiang Cong, Hu Qiangsheng, Jia Xinlin, Wang Shuqi, Wan Shiyue, Mao Yuanqing, Zhang Dapeng, Zhang Peng, Dai Bin, Li Yongsheng
Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontier Science Center of the Materials Biology and Dynamic Chemistry, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Nat Commun. 2025 Jan 6;16(1):424. doi: 10.1038/s41467-024-55658-0.
Reactive oxygen species (ROS) is promising in cancer therapy by accelerating tumor cell death, whose therapeutic efficacy, however, is greatly limited by the hypoxia in the tumor microenvironment (TME) and the antioxidant defense. Amplification of oxidative stress has been successfully employed for tumor therapy, but the interactions between cancer cells and the other factors of TME usually lead to inadequate tumor treatments. To tackle this issue, we develop a pH/redox dual-responsive nanomedicine based on the remodeling of cancer-associated fibroblasts (CAFs) for multi-pronged amplification of ROS (ZnPP@FQOS). It is demonstrated that ROS generated by ZnPP@FQOS is endogenously/exogenously multiply amplified owing to the CAFs remodeling and down-regulation of anti-oxidative stress in cancer cells, ultimately achieving the efficient photodynamic therapy in a female tumor-bearing mouse model. More importantly, ZnPP@FQOS is verified to enable the stimulation of enhanced immune responses and systemic immunity. This strategy remarkably potentiates the efficacy of photodynamic-immunotherapy, thus providing a promising enlightenment for tumor therapy.
活性氧（ROS）通过加速肿瘤细胞死亡在癌症治疗中具有广阔前景，然而，其治疗效果在很大程度上受到肿瘤微环境（TME）中的缺氧和抗氧化防御的限制。氧化应激的放大已成功应用于肿瘤治疗，但癌细胞与TME中其他因素之间的相互作用通常会导致肿瘤治疗不充分。为了解决这个问题，我们基于癌症相关成纤维细胞（CAF）的重塑开发了一种pH/氧化还原双响应纳米药物，用于多管齐下放大ROS（ZnPP@FQOS）。结果表明，由于CAF重塑和癌细胞中抗氧化应激的下调，ZnPP@FQOS产生的ROS在内源/外源性方面得到多重放大，最终在雌性荷瘤小鼠模型中实现了高效的光动力治疗。更重要的是，ZnPP@FQOS被证实能够刺激增强免疫反应和全身免疫。该策略显著增强了光动力免疫治疗的疗效，从而为肿瘤治疗提供了有前景的启示。
