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使用pHlexi纳米颗粒探究内体逃逸

Probing Endosomal Escape Using pHlexi Nanoparticles.

作者信息

Kongkatigumjorn Nachnicha, Cortez-Jugo Christina, Czuba Ewa, Wong Adelene S M, Hodgetts Rebecca Y, Johnston Angus P R, Such Georgina K

机构信息

School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia.

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia.

出版信息

Macromol Biosci. 2017 Apr;17(4). doi: 10.1002/mabi.201600248. Epub 2016 Oct 27.

Abstract

The effective escape of nanocarriers from endosomal compartments of the cell remains a major hurdle in nanomedicine. The endosomal escape of pH-responsive, self-assembled, dual component particles based on poly[2-(diethylamino)ethyl methacrylate)(PDEAEMA) and poly(ethylene glycol)-b-poly[2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) has been recently reported. Herein, we report that polymer molecular weight (M ) can be used to tune endosomal escape of nanoparticle delivery systems. PDEAEMA of M 7 kDa, 27 kDa, 56 kDa and 106 kDa was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and co-assembled with PEG-b-PDEAEMA (16 kDa) via nanoprecipitation. All particles had similar size, displayed pH-responsive behaviour, and low toxicity regardless of molecular weight. Ovalbumin was loaded in the particles to demonstrate loading and release capabilities and as a marker to study internalization and endosomal escape. Association and endosomal escape was found to depend on molecular weight, with enhanced escape observed for high M PDEAEMA: 42% of cells with particle induced endosomal escape for 106 kDa nanoparticles, compared to minimal escape for 7 kDa particles. The results show that a simple variation in molecular weight can enhance the endosomal escape of polymeric carriers, and thus improve their effectiveness for intracellular delivery of therapeutics.

摘要

纳米载体从细胞内体区室有效逃逸仍然是纳米医学中的一个主要障碍。最近有报道称基于聚2-(二乙氨基)乙基甲基丙烯酸酯和聚(乙二醇)-b-聚2-(二乙氨基)乙基甲基丙烯酸酯的pH响应性、自组装双组分颗粒可实现内体逃逸。在此,我们报告聚合物分子量(M)可用于调节纳米颗粒递送系统的内体逃逸。通过可逆加成-断裂链转移(RAFT)聚合反应合成了分子量分别为7 kDa、27 kDa、56 kDa和106 kDa的PDEAEMA,并通过纳米沉淀法与PEG-b-PDEAEMA(16 kDa)共组装。无论分子量如何,所有颗粒都具有相似的尺寸,表现出pH响应行为,且毒性较低。将卵清蛋白负载到颗粒中以展示负载和释放能力,并作为研究内化和内体逃逸的标记物。发现结合和内体逃逸取决于分子量,对于高分子量的PDEAEMA,内体逃逸增强:106 kDa纳米颗粒诱导42%的细胞发生颗粒诱导内体逃逸,而7 kDa颗粒的内体逃逸极少。结果表明,分子量的简单变化可以增强聚合物载体的内体逃逸,从而提高其在细胞内递送治疗剂的有效性。

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