Journal
RSC ADVANCES
Volume 3, Issue 43, Pages 19991-20000Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3ra42323a
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Funding
- NSF [CBET-0952624, CBET-1158447]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1158447] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0952624] Funding Source: National Science Foundation
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We synthesize and characterize two types of poly(N-hydroxyethyl acrylamide) (polyHEAA)-based nanogels: antifouling poly(2-(methacryloyloxy) ethyl trimethyl ammonium-g-N-hydroxyethyl acrylamide) (polyTM-g-HEAA) by a new two-step polymerization method of inverse microemulsion ATRP and surface-initiated atom transfer radical polymerization (SI-ATRP), and pH-responsive biodegradable polyHEAA nanogels by the inverse microemulsion free radical polymerization method. PolyTM-g-HEAA nanogels with a core-shell structure by grafting antifouling polyHEAA onto the cationic polyTM core are tested for their antifouling property and stability in fetal bovine serum (FBS) and nanogels-induced cell toxicity. Results show that with the antifouling protection of polyHEAA, polyTM-g-HEAA nanogels significantly improve their long-term stability in FBS up to 7 days by preventing nonspecific protein adsorption, and they also improve cell viability to similar to 94% and exhibit almost neglectable cell toxicity. Further, polyHEAA nanogels cross-linked with acid-liable ethylidenebis(oxy-2,1-ethanediyl) ester (EOE) are synthesized, which exhibit both biodegradation and control-release of encapsulated rhodamine 6G (R6G) at acid conditions. Conjugation of transferrin ligands onto R6G-loaded polyHEAA nanogels further enhances cellular uptake efficiency and intracellular drug release for targeting drug delivery. This work demonstrates that polyHEAA-based nanogels with easy synthesis, excellent antifouling property and stability, biodegradability, low toxicity, and pH-responsive intracellular drug release are highly promising for targeted drug delivery systems for biomedical applications.
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