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Sequence segregation improves non-covalent protein delivery.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 May 28; Vol. 254, pp. 131-136. Date of Electronic Publication: 2017 Mar 29. - Publication Year :
- 2017
-
Abstract
- The impermeability of the plasma membrane towards large, hydrophilic biomolecules is a major obstacle in their use and development against intracellular targets. To overcome such limitations, protein transduction domains (PTDs) have been used as protein carriers, however they often require covalent fusion to the protein for efficient delivery. In an effort to develop more efficient and versatile biological vehicles, a series of PTD-inspired polyoxanorbornene-based synthetic mimics with identical chemical compositions but different hydrophobic/hydrophilic segregation were used to investigate the role of sequence segregation on protein binding and uptake into Jurkat T cells and HEK293Ts. This series was composed of a strongly segregated block copolymer, an intermediately segregated gradient copolymer, and a non-segregated homopolymer. Among the series, the block copolymer maximized both protein binding and translocation efficiencies, closely followed by the gradient copolymer, resulting in two protein transporter molecules more efficacious than currently commercially available agents. These two polymers were also used to deliver the biologically active Cre recombinase into a loxP-reporter T cell line. Since exogenous Cre must reach the nucleus and retain its activity to induce gene recombination, this in vitro experiment better exemplifies the broad applicability of this synthetic system. This study shows that increasing segregation between hydrophobic and cationic moieties in these polymeric mimics improves non-covalent protein delivery, providing crucial design parameters for the creation of more potent biological delivery agents for research and biomedical applications.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Biological Transport
Drug Liberation
HEK293 Cells
Humans
Hydrophobic and Hydrophilic Interactions
Integrases metabolism
Jurkat Cells
Permeability
Protein Binding
Protein Conformation
Protein Domains
Proteins metabolism
Recombination, Genetic
Drug Carriers chemistry
Norbornanes chemistry
Peptides chemistry
Polymers chemistry
Proteins administration & dosage
Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 254
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 28363520
- Full Text :
- https://doi.org/10.1016/j.jconrel.2017.03.387