Abstract
Intracellular delivery of exogenous proteins is a field of bioscience that has grown rapidly in recent years, driven by the potential clinical applications. We developed a protein nanocarrier composed of amphiphilic polysaccharide nanogels formed by self-assembly of ethylenediamine- and cholesteryl group-bearing pullulan (CHP-NH2). The nanogel strongly interacts with cells allowing proteins to be internalized more effectively than with other carriers, such as cationic liposomes and a protein transduction domain-based amphiphilic peptide carrier. An interesting property of nanogels is that they can form a stable complex with proteins that are suitably sized suitable for intracellular uptake (~50 nm). Nanogels also act as artificial chaperones by preventing the aggregation of denatured protein and aid correct protein refolding. We also developed a cell-specific peptide (Arg-Gly-Asp; RGD)-modified nanogel (CHP-RGD) with greater potential for cell-specific, receptor-mediated delivery. This nanogel was effectively internalized into cells via integrin-mediated endocytosis, specifically clathrin-mediated endocytosis and macropinocytosis. Cell-specific peptide-modified polysaccharide nanogels are expected to have broad applications in drug delivery. In this chapter, we describe the results of recent studies and discuss future challenges for protein delivery using polysaccharide nanogels.
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Abbreviations
- RGD:
-
Arg-Gly-Asp
- BoHc:
-
Botulinus toxin
- CHP:
-
Cholesteryl group-bearing pullulan
- CHP-NH2 :
-
Ethylenediamine-bearing CHP
- PEG:
-
Polyethylene glycol
- PTD:
-
Protein transduction domain
- QD:
-
Quantum dot
- PEGSH:
-
Thiol group-bearing PEG
- W9 peptide:
-
WP9QY
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Shimoda, A., Sawada, Si., Akiyoshi, K. (2014). Intracellular Protein Delivery Using Self-Assembled Amphiphilic Polysaccharide Nanogels. In: Prokop, A., Iwasaki, Y., Harada, A. (eds) Intracellular Delivery II. Fundamental Biomedical Technologies, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8896-0_14
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DOI: https://doi.org/10.1007/978-94-017-8896-0_14
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