PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery
- PMID: 17497921
- DOI: 10.1021/bm070085x
PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery
Abstract
Under appropriate conditions, block copolymeric macroamphiphiles will self-assemble in water to form vesicles, referred to as polymersomes. We report here polymersomes that can protect biomolecules in the extracellular environment, are taken up by endocytosis, and then suddenly burst within the early endosome, releasing their contents prior to exposure to the harsh conditions encountered after lysosomal fusion. Specifically, block copolymers of the hydrophile poly(ethylene glycol) (PEG) and the hydrophobe poly(propylene sulfide) (PPS) were synthesized with an intervening disulfide, PEG17-SS-PPS30. Polymersomes formed from this block copolymer were demonstrated to disrupt in the presence of intracellular concentrations of cysteine. In cellular experiments, uptake, disruption, and release were observed within 10 min of exposure to cells, well within the time frame of the early endosome of endolysosomal processing. This system may be useful in cytoplasmic delivery of biomolecular drugs such as peptides, proteins, oligonucleotides, and DNA.
Similar articles
-
Aggregation behavior of poly(ethylene glycol-bl-propylene sulfide) di- and triblock copolymers in aqueous solution.Langmuir. 2009 Oct 6;25(19):11328-35. doi: 10.1021/la900649m. Langmuir. 2009. PMID: 19711914
-
PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release: cyclosporin A as an example.Mol Pharm. 2008 Jul-Aug;5(4):632-42. doi: 10.1021/mp7001297. Epub 2008 Jun 12. Mol Pharm. 2008. PMID: 18547055
-
Synthesis and in vitro characterization of an ABC triblock copolymer for siRNA delivery.Bioconjug Chem. 2007 May-Jun;18(3):736-45. doi: 10.1021/bc060284y. Epub 2007 Mar 15. Bioconjug Chem. 2007. PMID: 17358044
-
In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery.J Control Release. 2008 May 8;127(3):189-207. doi: 10.1016/j.jconrel.2008.01.005. Epub 2008 Jan 26. J Control Release. 2008. PMID: 18321604 Review.
-
Stimuli-responsive polymersomes as nanocarriers for drug and gene delivery.Macromol Biosci. 2009 Feb 11;9(2):129-39. doi: 10.1002/mabi.200800248. Macromol Biosci. 2009. PMID: 19107717 Review.
Cited by
-
Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines.J Nanobiotechnology. 2023 Nov 29;21(1):456. doi: 10.1186/s12951-023-02165-x. J Nanobiotechnology. 2023. PMID: 38017573 Free PMC article. Review.
-
Reduction-responsive polymeric micelles and vesicles for triggered intracellular drug release.Antioxid Redox Signal. 2014 Aug 10;21(5):755-67. doi: 10.1089/ars.2013.5733. Epub 2014 Feb 20. Antioxid Redox Signal. 2014. PMID: 24279980 Free PMC article. Review.
-
Exploiting endocytosis for nanomedicines.Cold Spring Harb Perspect Biol. 2013 Nov 1;5(11):a016980. doi: 10.1101/cshperspect.a016980. Cold Spring Harb Perspect Biol. 2013. PMID: 24186069 Free PMC article. Review.
-
Drug-Integrating Amphiphilic Nanomaterial Assemblies: 1. Spatiotemporal control of cyclosporine delivery and activity using nanomicelles and nanofibrils.J Control Release. 2021 Jan 10;329:955-970. doi: 10.1016/j.jconrel.2020.10.026. Epub 2020 Oct 18. J Control Release. 2021. PMID: 33086102 Free PMC article.
-
Reduction Sensitive Lipid Conjugates of Tenofovir: Synthesis, Stability, and Antiviral Activity.J Med Chem. 2016 Aug 11;59(15):7097-110. doi: 10.1021/acs.jmedchem.6b00428. Epub 2016 Jul 22. J Med Chem. 2016. PMID: 27405794 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
