Department of Chemistry, Kansas State University, Manhattan, KS, 66506, USA; Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS, 66506, USA; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, 66506, USA.
Department of Chemistry, Kansas State University, Manhattan, KS, 66506, USA; Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS, 66506, USA.
Biomaterials. 2018 Apr;160:124-137. doi: 10.1016/j.biomaterials.2018.01.018. Epub 2018 Jan 16.
Therapeutic efficacy of a systemic drug delivery largely depends on the targeting design of the delivery system, which tackles with circulatory traffic and prevents the nonspecific distribution of the drug in the wide range of vital organs. A drawing attention has been given to a biomimetic cloaking of the synthetic drug delivery nanoparticle using mammalian cell-ghosts, which has shown the installment of the biological complexity of the original cells thereby acting as naïve cells, to precisely delivery drug to the intended target. Align towards this direction; we developed a membrane camouflage fusogenic liposomal delivery system "NKsome" for targeted tumor therapy using Natural Killer (NK) cell-ghost, which naturally undergoes immunosurveillance of diseased/stress cells. The engineered NKsome shows successful retention of NK cell membrane-associated targeting protein on its surface. With its excellent biocompatibility, NKsome shows a higher affinity towards cancer than normal cells as demonstrated by in vitro flow-passage assay, and exhibits enhanced tumor homing efficiency in-vivo with an extended plasma residence time of 18 h. Moreover, the therapeutic potential of doxorubicin-loaded NKsome shows promising antitumor activity in vivo against MCF-7 induced tumor model. Overall results illustrate the therapeutic advantages of NK cell biomimicry capable of communicating like immune cells for cooperative drug delivery.
治疗效果在很大程度上取决于药物输送系统的靶向设计，该设计可以解决循环交通问题，并防止药物在广泛的重要器官中发生非特异性分布。人们越来越关注使用哺乳动物细胞-幽灵对合成药物输送纳米颗粒进行仿生伪装，这表明可以安装原始细胞的生物复杂性，从而充当原始细胞，将药物精确地输送到预期的靶标。为了实现这一目标；我们开发了一种膜伪装融合脂质体输送系统“NKsome”，用于使用自然杀伤 (NK) 细胞-幽灵进行靶向肿瘤治疗，该系统可自然对患病/应激细胞进行免疫监视。工程化的 NKsome 显示出成功保留了其表面上的 NK 细胞膜相关靶向蛋白。由于其出色的生物相容性，与正常细胞相比，NKsome 对癌症具有更高的亲和力，如体外流通过程测定所示，并表现出增强的肿瘤归巢效率，体内血浆半衰期延长至 18 小时。此外，载有阿霉素的 NKsome 的治疗潜力在体内对 MCF-7 诱导的肿瘤模型显示出有希望的抗肿瘤活性。总体结果说明了能够像免疫细胞一样进行通信的 NK 细胞仿生的治疗优势，可用于协同药物输送。
