Department of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University.
Department of Pharmaceutical Health Chemistry, Graduate School of Biomedical Sciences, Tokushima University.
Chem Pharm Bull (Tokyo). 2022;70(5):334-340. doi: 10.1248/cpb.c21-00961.
Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.
利用纳米颗粒进行靶向药物输送已应用于治疗多种疾病，包括癌症和炎症性疾病。通过增强通透性和保留效应，纳米颗粒介导的治疗剂输送通常会提高其治疗效率；然而，由于内皮层等生物屏障的存在，纳米颗粒被动进入病变部位的局限性仍然存在。为此，开发具有类似于循环细胞（如白细胞、血小板）内在特性的纳米颗粒作为仿生药物输送系统（DDS）已成为克服传统 DDS 问题的一种手段。特别是，最近制备了涂有细胞膜的合成仿生纳米颗粒，并显示出由于膜蛋白的功能而能够主动克服炎症血管和肿瘤微环境，从而能够安全地将药物输送到病变部位。我们最近通过膜间蛋白转移开发了用白细胞膜蛋白修饰的脂质体，这是一种将细胞膜蛋白重新构成脂质双层的简单方法。结果表明，这些脂质体能够模拟白细胞的特性，穿过炎症内皮层并渗透到肿瘤组织中。因此，仿生 DDS 通过克服通常抑制药物输送的生物屏障，为各种疾病提供了有前途的新治疗方法。在此，我们综述了使用细胞膜涂层方法开发仿生 DDS 的最新方法，并重点介绍了我们通过膜间蛋白转移制备的白细胞模拟脂质体的最新发现。
