Endoprotease-mediated intracellular protein delivery using nanocapsules.
Proteins possess distinct intracellular roles allowing them to have vast therapeutic applications. However, due to poor cellular permeability and fragility of most proteins, intracellular delivery of native, active proteins is challenging. We describe a biomimetic protein delivery vehicle which is degradable upon the digestion by furin, a ubiquitous intracellular protease, to release encapsulated cargos. Proteins were encapsulated in a nanosized matrix prepared with monomers and a bisacrylated peptide cross-linker which can be specifically recognized and cleaved by furin. Release of encapsulated protein was confirmed in a cell-free system upon proteolytic degradation of nanocapsules. In vitro cell culture studies demonstrated successful intracellular delivery of both nuclear and cytosolic proteins and confirmed the importance of furin-degradable construction for native protein release. This endoprotease-mediated intracellular delivery system may be extended to effectively deliver various biological therapeutics.
Department of Chemical and Biomolecular Engineering, University of California at Los Angeles, Los Angeles, California 90095, USA.
Anuradha
A
Biswas
Kye-Il
KI
Joo
Jing
J
Liu
Muxun
M
Zhao
Guoping
G
Fan
Pin
P
Wang
Zhen
Z
Gu
Yi
Y
Tang
D000818:Animals; D040761:Biomimetic Materials; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D045683:Furin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D053769:Nanocapsules; D011487:Protein Conformation; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D053769:Nanocapsules; D011506:Proteins; D045683:Furin