State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and Jiangsu Key Laboratory of Drug Design and Optimization, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
ACS Nano. 2024 Oct 15;18(41):28081-28094. doi: 10.1021/acsnano.4c07341. Epub 2024 Oct 3.
A cell membrane-derived vesicle (MV) that has cell-mimicking features with characteristic functionalities holds vast appeal for biomimetic nanomedicine and drug delivery but suffers from a major limitation of innate fragility and poor stability. Herein, we report a lipid-anchoring strategy for stabilizing MV for enhanced drug delivery. An array of amphiphilic mono-acyl phosphatidylcholines (MPCs) with specific hydrophobic moieties are synthesized and readily engineered on MV based on their commendable aqueous solubility and efficient membrane insertability. Incorporation of MPCs containing rigid ring structures in the hydrophobic segment demonstrates the potency of stabilizing MV by the combined ordering and condensing effects. The optimized MPC-stabilized MV exhibits prolonged circulation in the bloodstream, elevated accumulation within a tumor, and enhanced therapeutic effects of chemotherapeutic and photothermal drugs. Moreover, doxorubicin-loaded MV, engineered with mono-all- retinoyl phosphatidylcholine as an MV stabilizer and a therapeutic prodrug, potently suppresses growth and metastasis of high-stemness tumors.
细胞膜衍生囊泡（MV）具有细胞模拟特性和特征性功能，对仿生纳米医学和药物输送具有巨大的吸引力，但存在固有脆弱性和较差稳定性的主要限制。在此，我们报告了一种稳定 MV 的脂质锚定策略，以增强药物输送。一系列具有特定疏水性部分的两亲性单酰基磷脂酰胆碱（MPC）已被合成，并根据其出色的水溶性和高效的膜插入能力，基于其在 MV 上进行了易于设计。在疏水区段中包含刚性环结构的 MPC 的掺入表明通过组合的有序化和浓缩效应稳定 MV 的效力。优化的 MPC 稳定的 MV 在血液中表现出延长的循环时间，在肿瘤内的积累增加，以及化疗和光热药物的治疗效果增强。此外，用单全视黄酰基磷脂酰胆碱作为 MV 稳定剂和治疗前药设计的载多柔比星 MV 能够有力地抑制高干性肿瘤的生长和转移。
