Hypoxia tumor microenvironment is a major challenge for photodynamical therapy (PDT), and hypoxia-activated chemotherapy combined PDT could be promising for enhanced anticancer therapy. In this study, we report an innovative 2-nitroimidazole derivative conjugated polyethylene glycol (PEG) amphoteric polymer theranostic liposome encapsulated a photosensitizer Chlorin e6 (Ce6), hypoxia-activated prodrug Tirapazamine (TPZ) and gene probe for synergistic photodynamic-chemotherapy. Ce6-mediated PDT upon irradiation with a laser induces hypoxia, which leads to the disassembly of the liposome and activates the antitumor activity of TPZ for improved cancer cell-killing. The released co-delivered gene probe could effectively detect the oncogenic intracellular biomarker for diagnosis. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional PDT. This work contributes to the design of hypoxia-responsive multifunctional liposome for tumor diagnosis and hypoxia-activated chemotherapy combined PDT for synergetic therapy, which holds great promise for future cancer therapy.

缺氧肿瘤微环境是光动力疗法（PDT）的主要挑战，缺氧激活化疗联合PDT有望增强抗癌治疗。在这项研究中，我们报告了创新的2-硝基咪唑衍生物共轭聚乙二醇（PEG）两性聚合物治疗核糖体，包裹了光敏剂Chlorin e6（Ce6），低氧激活的前药Tirapazamine（TPZ）和用于协同光动力化学疗法的基因探针。Ce6介导的PDT在激光照射下会引起缺氧，这会导致脂质体的分解并激活TPZ的抗肿瘤活性，从而改善癌细胞的杀伤力。释放的共同递送基因探针可以有效地检测致癌细胞内生物标志物以进行诊断。体外和体内研究均表明，与常规PDT相比，抗癌活性大大提高。这项工作为设计用于肿瘤诊断的低氧反应性多功能脂质体和用于协同治疗的低氧激活化疗联合PDT的设计做出了贡献，这为未来的癌症治疗提供了广阔的前景。