Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology and ‡Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University , Wuhan, Hubei 430072, China.
Department of Biomedical Engineering and ⊥Department of Mechanical Engineering, Johns Hopkins University , Baltimore, Maryland 21218, United States.
ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2159-2168. doi: 10.1021/acsami.6b14450. Epub 2017 Jan 12.
Upconversion nanoparticles (UCNPs) with superior optical and chemical features have been broadly employed for in vivo cancer imaging. Generally, UCNPs are surface modified with ligands for cancer active targeting. However, nanoparticles in biological fluids are known to form a long-lived "protein corona", which covers the targeting ligands on nanoparticle surface and dramatically reduces the nanoparticle targeting capabilities. Here, for the first time, we demonstrated that by coating UCNPs with red blood cell (RBC) membranes, the resulting cell membrane-capped nanoparticles (RBC-UCNPs) adsorbed virtually no proteins when exposed to human plasma. We further observed in various scenarios that the cancer targeting ability of folic acid (FA)-functionalized nanoparticles (FA-RBC-UCNPs) was rescued by the cell membrane coating. Next, the FA-RBC-UCNPs were successfully utilized for enhanced in vivo tumor imaging. Finally, blood parameters and histology analysis suggested that no significant systematic toxicity was induced by the injection of biomimetic nanoparticles. Our method provides a new angle on the design of targeted nanoparticles for biomedical applications.
上转换纳米粒子（UCNPs）具有优异的光学和化学特性，已广泛应用于体内癌症成像。通常，UCNPs 表面用配体进行修饰以实现癌症主动靶向。然而，人们知道，在生物流体中的纳米粒子会形成一种持久的“蛋白质冠”，覆盖纳米粒子表面的靶向配体，从而大大降低了纳米粒子的靶向能力。在这里，我们首次证明，通过用红细胞（RBC）膜包裹 UCNPs，所得的细胞膜包裹的纳米粒子（RBC-UCNPs）在与人血浆接触时几乎不吸附蛋白质。我们进一步在各种情况下观察到，通过细胞膜涂层，叶酸（FA）功能化纳米粒子（FA-RBC-UCNPs）的癌症靶向能力得到了恢复。接下来，FA-RBC-UCNPs 成功地用于增强体内肿瘤成像。最后，血液参数和组织学分析表明，注射仿生纳米粒子不会引起明显的系统毒性。我们的方法为生物医学应用中靶向纳米粒子的设计提供了一个新的视角。
