School of Life Sciences , Shanghai University , No. 333 Nanchen Road , Baoshan District, Shanghai 200444 , China.
CAS Key Laboratory of Bio-Medical Diagnostics , Suzhou Institute of Biomedical Engineering and Technology (SIBET) , No. 88 Keling Road , Suzhou New District , 215163 Jiangsu Province , China.
ACS Appl Mater Interfaces. 2018 Jul 11;10(27):22963-22973. doi: 10.1021/acsami.8b05363. Epub 2018 Jun 26.
Multiple cell plasma membranes have been utilized for surface functionalization of synthetic nanomaterials and construction of biomimetic drug delivery systems for cancer treatment. The natural characters and facile isolation of original cells facilitate the biomedical applications of plasma membranes in functionalizing nanocarriers. Human umbilical cord-derived mesenchymal stem cells (MSCs) have been identified to show tropism toward malignant lesions and have great advantages in ease of acquisition, low immunogenicity, and high proliferative ability. Here, we developed a poly(lactic- co-glycolic acid) (PLGA) nanoparticle with a layer of plasma membrane from umbilical cord MSC coating on the surface for tumor-targeted delivery of chemotherapy. Functionalization of MSC plasma membrane significantly enhanced the cellular uptake efficiency of PLGA nanoparticles, the tumor cell killing efficacy of PLGA-encapsulated doxorubicin, and most importantly the tumor-targeting and accumulation of the nanoparticles. As a result, this MSC-mimicking nanoformulation led to remarkable tumor growth inhibition and induced obvious apoptosis within tumor lesions. This study for the first time demonstrated the great potential of umbilical cord MSC plasma membranes in functionalizing nanocarriers with inherent tumor-homing features and the high feasibility of such biomimetic nanoformulations in cancer therapy.
已经利用多种细胞膜对合成纳米材料进行表面功能化，并构建仿生药物输送系统用于癌症治疗。原始细胞的天然特性和易于分离促进了细胞膜在功能化纳米载体中的生物医学应用。已经确定人脐带间充质干细胞（MSCs）对恶性病变具有趋向性，并且在获取、低免疫原性和高增殖能力方面具有巨大优势。在这里，我们开发了一种聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒，其表面涂有一层来自脐带 MSC 的细胞膜，用于化疗的肿瘤靶向递药。MSC 细胞膜的功能化显著提高了 PLGA 纳米颗粒的细胞摄取效率、PLGA 包封阿霉素的肿瘤细胞杀伤效力，最重要的是提高了纳米颗粒的肿瘤靶向性和积累。结果，这种 MSC 模拟的纳米制剂导致显著的肿瘤生长抑制，并在肿瘤病变中诱导明显的细胞凋亡。这项研究首次证明了脐带 MSC 细胞膜在赋予具有内在肿瘤归巢特性的纳米载体功能方面的巨大潜力，以及这种仿生纳米制剂在癌症治疗中的高度可行性。
