Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, 230027, Hefei, Anhui, China.
Intelligent Nanomedicine Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, China.
Nat Commun. 2020 Feb 28;11(1):1126. doi: 10.1038/s41467-020-14963-0.
The efficacy of nano-mediated drug delivery has been impeded by multiple biological barriers such as the mononuclear phagocyte system (MPS), as well as vascular and interstitial barriers. To overcome the abovementioned obstacles, we report a nano-pathogenoid (NPN) system that can in situ hitchhike circulating neutrophils and supplement photothermal therapy (PTT). Cloaked with bacteria-secreted outer membrane vesicles inheriting pathogen-associated molecular patterns of native bacteria, NPNs are effectively recognized and internalized by neutrophils. The neutrophils migrate towards inflamed tumors, extravasate across the blood vessels, and penetrate through the tumors. Then NPNs are rapidly released from neutrophils in response to inflammatory stimuli and subsequently taken up by tumor cells to exert anticancer effects. Strikingly, due to the excellent targeting efficacy, cisplatin-loaded NPNs combined with PTT completely eradicate tumors in all treated mice. Such a nano-platform represents an efficient and generalizable strategy towards in situ cell hitchhiking as well as enhanced tumor targeted delivery.
纳米递药的疗效受到多种生物屏障的阻碍，如单核吞噬细胞系统（MPS）以及血管和细胞间质屏障。为了克服上述障碍，我们报告了一种纳米病原体样颗粒（NPN）系统，该系统可以原位搭乘循环中的中性粒细胞并补充光热疗法（PTT）。NPN 被细菌分泌的具有天然细菌相关分子模式的外膜囊泡包裹，可被中性粒细胞有效识别和内化。中性粒细胞向炎症肿瘤迁移，穿过血管渗出，并穿透肿瘤。然后，NPN 会响应炎症刺激从中性粒细胞中迅速释放，并随后被肿瘤细胞摄取以发挥抗癌作用。引人注目的是，由于优异的靶向效果，载顺铂的 NPN 与 PTT 联合使用可完全消除所有治疗小鼠的肿瘤。这种纳米平台代表了一种高效且可推广的原位细胞搭乘以及增强肿瘤靶向递药策略。
