Xie Xinran, Zhang Shuaiyin, Liu Ming, Ye Yang, Huang Yongxin, Li Zhixin, Lin Junyan, Liu Jie, Zhou Jingchun, Xu Changyi, Tu Zhaoxu
Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
Department of Otolaryngology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
J Mater Chem B. 2025 Jul 16;13(28):8380-8394. doi: 10.1039/d5tb00801h.
Photodynamic therapy (PDT) has emerged as a promising non-invasive therapeutic modality for tumor treatment. Moreover, PDT has the potential to induce immunogenic cell death (ICD), and its combination with immunotherapeutic strategies has become a promising approach for tumor therapy. In this study, we designed a multifunctional nanoplatform, IR@BP-L, which integrates PDT-induced pyroptosis with loxoribine as an immune agonist. On one hand, the effective accumulation of IR@BP-L at the tumor site enables PDT treatment near-infrared light irradiation, generating a large amount of reactive oxygen species (ROS) to induce pyroptosis and promote local immunity. On the other hand, loxoribine is responsively released under near-infrared light irradiation and within the weakly acidic tumor microenvironment, thereby enhancing immune activation at the tumor site. As a TLR7 agonist, loxoribine effectively stimulates dendritic cell maturation, thereby potentiating T cell-dependent antitumor immunity. This co-delivery system amplifies immune activation by combining PDT-induced pyroptosis with immune agonist, leading to more effective antitumor outcomes. The nanoplatform demonstrated excellent immune activation effects and the ability to reverse the immunosuppressive tumor microenvironment after intravenous administration. Our strategy offered valuable insights for the development of a synergistic strategy for cancer immunotherapy.
光动力疗法（PDT）已成为一种很有前景的肿瘤非侵入性治疗方式。此外，PDT有诱导免疫原性细胞死亡（ICD）的潜力，并且它与免疫治疗策略的联合已成为一种很有前景的肿瘤治疗方法。在本研究中，我们设计了一种多功能纳米平台IR@BP-L，它将PDT诱导的细胞焦亡与作为免疫激动剂的洛索立宾整合在一起。一方面，IR@BP-L在肿瘤部位的有效积累使得在近红外光照射下进行PDT治疗，产生大量活性氧（ROS）以诱导细胞焦亡并促进局部免疫。另一方面，洛索立宾在近红外光照射下以及在弱酸性肿瘤微环境中响应性释放，从而增强肿瘤部位的免疫激活。作为一种Toll样受体7（TLR7）激动剂，洛索立宾有效刺激树突状细胞成熟，从而增强T细胞依赖性抗肿瘤免疫。这种共递送系统通过将PDT诱导的细胞焦亡与免疫激动剂相结合来放大免疫激活，导致更有效的抗肿瘤效果。该纳米平台在静脉给药后表现出优异的免疫激活作用以及逆转免疫抑制性肿瘤微环境的能力。我们的策略为开发癌症免疫治疗的协同策略提供了有价值的见解。
