Abstract：
Sub-50 nm nanoparticles feature long circulation and deep tumor penetration. However, at high volume fractions needed for intravenous injection, safe, highly biocompatible phospholipids cannot form such nanoparticles due to the fluidity of phospholipid shells. Here we overcome this challenge using a nano-surfactant, a sterilized 18-amino-acid biomimetic of the amphipathic helical motif abundant in HDL-apolipoproteins. As it induces a nanoscale phase (glass) transition in the phospholipid monolayer, the peptide stabilizes 5-7 nm phospholipid micelles that do not fuse at high concentrations but aggregate into stable micellesomes exhibiting size-dependent penetration into tumors. In mice bearing human Her-2-positive breast cancer xenografts, high-payload paclitaxel encapsulated in 25 nm (diameter) micellesomes kills more cancer cells than paclitaxel in standard clinical formulation, as evidenced by the enhanced apparent diffusion coefficient of water determined by in vivo MR imaging. Importantly, the bio-inertness of this biomimetic nano-surfactant spares the nanoparticles from being absorbed by liver hepatocytes, making them more generally available for drug delivery.
摘要：
亚50nm纳米粒子具有长循环和深肿瘤渗透的特征。然而,在静脉注射所需的高体积分数下，安全,由于磷脂壳的流动性,高度生物相容性的磷脂不能形成这样的纳米颗粒。在这里，我们使用纳米表面活性剂克服了这个挑战，HDL载脂蛋白中丰富的两亲性螺旋基序的18个氨基酸的灭菌仿生。由于它在磷脂单层中诱导纳米级相（玻璃）转变，该肽稳定5-7nm的磷脂胶束，这些胶束在高浓度下不融合，但聚集成稳定的胶束，表现出大小依赖性渗透到肿瘤中。在携带人类Her-2阳性乳腺癌异种移植物的小鼠中，封装在25nm（直径）胶束中的高有效载荷紫杉醇比标准临床制剂中的紫杉醇杀死更多的癌细胞，通过体内MR成像确定的水的表观扩散系数增强证明了这一点。重要的是,这种仿生纳米表面活性剂的生物惰性避免了纳米颗粒被肝细胞吸收，使它们更普遍地用于药物输送。
