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《化学科学与工程前沿(英文)》 >> 2014年 第8卷 第4期 doi: 10.1007/s11705-014-1457-3

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs: learning from virus

Department of Pharmaceutical Sciences, University of Nebraska Medical Center (UNMC), Omaha, NE 68198-6025, USA

录用日期: 2014-12-30 发布日期: 2015-01-14

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摘要

There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.

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