光动力学治疗（PDT）因其侵袭性小，时空选择性高，被广泛应用于抗肿瘤治疗。然而，光的组织穿透深度不足往往限制了其抗肿瘤疗效。免疫治疗协同PDT的策略可以解决这个问题。但是肿瘤的微酸环境和乏氧环境会改变免疫细胞功能，抑制其活性，极大地阻碍了协同治疗策略的治疗效率。基于此，本项目拟使用过氧化铜纳米粒子作为能够消耗肿瘤区域氢离子并产生氧气的碱性材料，使用红细胞膜对其进行生物仿生修饰，最后使用具有PDT功能的嵌合肽C16-PpIX（C16-K(PpIX)RRRR）修饰红细胞膜，构建具有逆转肿瘤微环境功能的高效PDT纳米体系。本项目将通过逆转肿瘤微酸环境、乏氧环境激活免疫细胞协同PDT的作用机制实现同时抑制原位肿瘤以及远端肿瘤的生长。本项目的开展将为新型免疫治疗协同的高效PDT策略的构建提供新的思路。

Photodynamic therapy (PDT) is widely used in antitumor therapy due to its low invasiveness and high spatiotemporal selectivity. However, insufficient tissue penetration depth of the light often limits its antitumor efficacy. The strategy that immunotherapy combined with PDT can solve the problem, but the tumor micro-acid and hypoxic environment could change the function of immune cells and inhibit their activity, which greatly hinders the efficiency of synergistic strategies. Here, in this project, a high-efficiency PDT nanosystem with the function of reversing the tumor microenvironment will be constructed. The copper peroxide is used as alkaline material to reverse the tumor micro-acid and hypoxic environment, and biomimetically modified with red blood cell membranes which are inserted with the chimeric peptide C16-PpIX(C16-K(PpIX)RRRR). The project will achieve the simultaneous inhibition of tumor growth in situ and distant tumors by mechanism of reversing the tumor micro-acid and hypoxic environment, which could activate immune cells and improve PDT. The development of the project would provide new ideas for the construction of strategy that contains the synergistic therapy with PDT and immunotherapy.