Nanomedicine which delivers therapeutics to tumours holds great potential for cancer treatment. However, endosomal trapping and uncontrollable release usually limit the efficiency of nanomedicine. Herein, a smart mesoporous silica based nanoplatform was constructed, in which mesoporous silica nanoparticles (MSNs) serve as the core, capped with pH-induced charge-reversal polymer -PAH-cit- and cationic polyelectrolyte polyethyleneimine (PEI). The oppositely charged polymer can not only act as a gatekeeper for controlled release, but also mediated efficient endosomal escape of the therapeutics. Under the acidic endosomal environment, the hydrolysis of acid-cleavable bonds in PAH-Cit would trigger the charge reversal and endosomal escape of the nanoplatform for efficient drug release. Furthermore, the prepared nanoplatform demonstrated a higher tumor cell proliferation inhibition rate than free theruputics in vitro assays and significantly inhibited tumour growth in the 4T1 tumour model in mice. Therefore, our strategy offers a simple and general nanoplatform to delivery therapeutics to tumours with efficient endosomal escape and controlled release.

为肿瘤提供治疗的纳米医学在癌症治疗方面具有巨大潜力。然而，内体捕获和无法控制的释放通常限制了纳米医学的效率。在此，构建了一个基于介孔二氧化硅的智能纳米平台，其中介孔二氧化硅纳米粒子 (MSNs) 作为核心，用 pH 诱导的电荷反转聚合物 -PAH-cit- 和阳离子聚电解质聚乙烯亚胺 (PEI) 封端。带相反电荷的聚合物不仅可以作为控释的看门人，还可以介导治疗剂的有效内体逃逸。在酸性内体环境下，多环芳烃-Cit 中酸可裂解键的水解将触发纳米平台的电荷反转和内体逃逸，以实现有效的药物释放。此外，制备的纳米平台在体外试验中表现出比游离治疗剂更高的肿瘤细胞增殖抑制率，并显着抑制了小鼠 4T1 肿瘤模型中的肿瘤生长。因此，我们的策略提供了一个简单而通用的纳米平台，以有效的内体逃逸和控制释放向肿瘤递送治疗剂。