Journal
BIOMACROMOLECULES
Volume 21, Issue 10, Pages 4313-4325Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.0c01113
Keywords
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Funding
- Spanish Ministerio de Ciencia, InnovaciOn y Universidades [MAT2017-82669-R]
- FPI [BES-2015-072662]
- Serra Hunter Programme of the Government of Catalonia
- Miguel Servet Program from Instituto de Salud Carlos III [CPII13/00017]
- Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III
- European Union (ERDF/ESF, `Investing in your future') [PI18/00343]
- DiputaciOn General de Aragon [B25_20R]
- Centro de InvestigaciOn Biomedica en Red en Enfermedades Hepaticas y Digestivas (CIBERehd)
- National Science Foundation [DMR1066116, DMR-1807127]
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Well-defined hydrophilic telechelic dibromo poly(triethylene glycol monomethyl ether acrylate)s were prepared by single-electron transfer living radical polymerization employing a hydrophobic difunctional initiator containing acetal and disulfide linkages. Although the resulting homopolymers have low hydrophobic contents (<8.5 wt % of the entire structure), they are able to self-assemble in water into nanoscale micellelike particles via chain folding. Acetal and disulfide linkages were demonstrated to be keystone units for their dual stimuli-responsive behavior under biochemically relevant conditions. Their site-selective middle-chain cleavage under both acidic pH and reductive conditions splits the homopolymer into two equal-sized fragments and results in the breakdown of the nanoassemblies. The drug loading/delivery potential of these nanoparticles was investigated using curcumine combining in vitro drug release, cytotoxicity, and cellular uptake studies with human cancer cell lines (HT-29 and HeLa). Importantly, this strategy may be extended to prepare innovative nanoplatforms based on hydrophilic homopolymers or random copolymers for intelligent drug delivery.
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