State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.
Angew Chem Int Ed Engl. 2021 Jun 14;60(25):14013-14021. doi: 10.1002/anie.202102059. Epub 2021 May 11.
The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.
肿瘤中细菌的存在会导致癌症对化疗药物产生耐药性。为了对抗细菌诱导的药物耐药性，我们设计了具有自我追踪能力的纳米储库，同时装载了吉西他滨（一种抗癌药物）和环丙沙星（一种抗生素），并通过透明质酸进行修饰以实现主动肿瘤靶向。纳米储库具有 pH 敏感的门控和酶响应的门控，可以在酸性和透明质酸酶丰富的肿瘤微环境中打开，以控制药物释放率。此外，纳米储库可以特异性地靶向肿瘤区域，而不会对正常组织产生明显的毒性，杀死肿瘤内的细菌，并抑制肿瘤生长，即使在存在细菌的情况下也是如此。出乎意料的是，纳米储库可以通过促进抗原呈递树突状细胞成熟和耗尽细菌感染肿瘤中的免疫抑制髓样来源抑制细胞来激活 T 细胞介导的免疫反应。
