Zhang Cuiyun, Shi Yiqi, Zhu Zhirong, Yang Ting, Wang Yuwei, Hu Shanshan, Wu Qi, Yang Haojian, Liu Jihong, Zhu Wei-Hong, Wang Qi
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Shanghai Key Laboratory of Functional Materials Chemistry, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P.R. China.
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, P.R. China.
ACS Nano. 2025 Apr 1;19(12):12119-12137. doi: 10.1021/acsnano.4c18518. Epub 2025 Mar 19.
Cell membrane-coated nanoparticle-based delivery systems often struggle with inevitable drug leakage during the delivery process and inefficient drug release at the tumor site, resulting in unsatisfactory antitumor outcomes. Here, we present an electrostatically stabilized light-activated membrane delivery system (Hybrid membrane nanoparticles, [Hm]@NPs) for leak-free drug delivery, coupled with precisely site-specific and controllable drug release, to elevate cancer treatment. [Hm]@NPs are constructed by encapsulating an aggregation-induced emission (AIE) photosensitizer (Phenalen-1-one-quinoline malonitrile-thiophene tribenamine, Phe-Qui-T) into a positively charged reactive oxygen species (ROS)-responsive polymer (F127-TP-U11) to form a positively charged nanoparticle and then coating it with a negatively charged hybrid membrane containing red blood cell membrane and Panc-1 cell membrane. [Hm]@NPs with high stability effectively prevent drug leakage through electrostatic interaction between the hybrid membrane and nanoparticle. Simultaneously, the photosensitizer Phe-Qui-T with light-controlled ROS generation efficiently destroys both the ROS-responsive polymer and the hybrid membrane, ensuring precise and sufficient drug release while enabling photodynamic therapy (PDT), thereby augmenting antitumor efficacy. [Hm]@NPs show impressive tumor inhibition in pancreatic cancer mouse models, highlighting the potential of this light-controlled membrane-disruption strategy for advanced cell membrane-coated nanodelivery system design.
基于细胞膜包裹的纳米颗粒递送系统在递送过程中常常难以避免药物泄漏，且在肿瘤部位药物释放效率低下，导致抗肿瘤效果不尽人意。在此，我们提出一种静电稳定的光激活膜递送系统（混合膜纳米颗粒，[Hm]@NPs），用于无泄漏药物递送，并结合精确的位点特异性和可控药物释放，以提升癌症治疗效果。[Hm]@NPs的构建方法是，将一种聚集诱导发光（AIE）光敏剂（菲-1-酮-喹啉丙二腈-噻吩三苯胺，Phe-Qui-T）封装到带正电荷的活性氧（ROS）响应聚合物（F127-TP-U11）中，形成带正电荷的纳米颗粒，然后用含有红细胞膜和Panc-1细胞膜的带负电荷的混合膜进行包裹。具有高稳定性的[Hm]@NPs通过混合膜与纳米颗粒之间的静电相互作用有效防止药物泄漏。同时，具有光控ROS生成能力的光敏剂Phe-Qui-T能有效破坏ROS响应聚合物和混合膜，确保精确且充分的药物释放，同时实现光动力疗法（PDT），从而增强抗肿瘤疗效。[Hm]@NPs在胰腺癌小鼠模型中显示出令人印象深刻的肿瘤抑制效果，突出了这种光控膜破坏策略在先进的细胞膜包裹纳米递送系统设计中的潜力。
