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

Abstract

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.

Key words： nanocarrier; cellular uptake; endosomal release; nucleic acid drug

Acknowledgements

The National Institutes of Health (1R01EB017853), Fred and Pamela Buffet Cancer Center and Cattlemen’s Ball of Nebraska, Inc. are duly acknowledged for providing financial support for this work. We also acknowledge the Faculty Start-up fund to Ram Mahato from the University of Nebraska Medical Center.

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