Protein Delivery into the Cell Cytosol using Non-Viral Nanocarriers

Yi-Wei Lee¹, David C. Luther¹, Jessica A. Kretzmann^1,2, Andrew Burden¹, Taewon Jeon^1,3, Shumei Zhai^1,4, Vincent M. Rotello^1✉

1. Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St., Amherst, USA.
2. School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
3. Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 710 N. Pleasant St., Amherst, USA.
4. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China.

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Citation:
Lee YW, Luther DC, Kretzmann JA, Burden A, Jeon T, Zhai S, Rotello VM. Protein Delivery into the Cell Cytosol using Non-Viral Nanocarriers. Theranostics 2019; 9(11):3280-3292. doi:10.7150/thno.34412. Available from https://www.thno.org/v09p3280.htm

Abstract

Protein delivery into cells is a potentially transformative tool for treating “undruggable” targets in diseases associated with protein deficiencies or mutations. The vast majority of these targets are accessed via the cytosol, a challenging prospect for proteins with therapeutic and diagnostic relevance. In this review we will present promising non-viral approaches for intracellular and ultimately cytosolic delivery of proteins using nanocarriers. We will also discuss the mechanistic properties that govern the efficacy of nanocarrier-mediated protein delivery, applications of nanomaterials, and key challenges and opportunities in the use of nanocarriers for intracellular protein delivery.

Keywords: intracellular protein delivery, supramolecular assemblies, protein therapeutics, endosomal escape, membrane fusion