Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
Department of Materials Science and Engineering , University of Illinois at Urbana-Champaign , Urbana , Illinois 61801 , United States.
Nano Lett. 2018 Mar 14;18(3):1908-1915. doi: 10.1021/acs.nanolett.7b05263. Epub 2018 Feb 23.
Various delivery vectors have been integrated within biologically derived membrane systems to extend their residential time and reduce their reticuloendothelial system (RES) clearance during systemic circulation. However, rational design is still needed to further improve the in situ penetration efficiency of chemo-drug-loaded membrane delivery-system formulations and their release profiles at the tumor site. Here, a macrophage-membrane-coated nanoparticle is developed for tumor-targeted chemotherapy delivery with a controlled release profile in response to tumor microenvironment stimuli. Upon fulfilling its mission of tumor homing and RES evasion, the macrophage-membrane coating can be shed via morphological changes driven by extracellular microenvironment stimuli. The nanoparticles discharged from the outer membrane coating show penetration efficiency enhanced by their size advantage and surface modifications. After internalization by the tumor cells, the loaded drug is quickly released from the nanoparticles in response to the endosome pH. The designed macrophage-membrane-coated nanoparticle (cskc-PPiP/PTX@Ma) exhibits an enhanced therapeutic effect inherited from both membrane-derived tumor homing and step-by-step controlled drug release. Thus, the combination of a biomimetic cell membrane and a cascade-responsive polymeric nanoparticle embodies an effective drug delivery system tailored to the tumor microenvironment.
各种输送载体已被整合到生物衍生的膜系统中，以延长其在体内的停留时间，并减少其在全身循环过程中被网状内皮系统（RES）清除的速度。然而，仍需要进行合理的设计，以进一步提高载药膜输送系统制剂的原位渗透效率，并改善其在肿瘤部位的释放特性。在这里，开发了一种巨噬细胞膜包裹的纳米颗粒，用于肿瘤靶向化疗输送，具有对肿瘤微环境刺激的控制释放特性。在完成肿瘤归巢和逃避 RES 的任务后，巨噬细胞膜涂层可以通过细胞外微环境刺激驱动的形态变化而脱落。从外膜涂层中排出的纳米颗粒由于其尺寸优势和表面修饰而表现出增强的穿透效率。进入肿瘤细胞后，载药纳米颗粒会迅速响应内涵体 pH 值从纳米颗粒中释放出来。设计的巨噬细胞膜包裹的纳米颗粒（cskc-PPiP/PTX@Ma）具有从膜衍生的肿瘤归巢和逐步控制药物释放中继承的增强治疗效果。因此，仿生细胞膜和级联响应聚合物纳米颗粒的结合体现了一种针对肿瘤微环境的有效药物输送系统。
