Ca2+-Chelation-Induced Fabrication of Multistimuli-Responsive Charged Nanogels from Phospholipid-Polymer Conjugates and Use for Drug/Protein Loading

Thermoresponsive phospholipid-poly(N-isopropylacrylamide) (PL-PNIPAM) conjugates were synthesized via reversible addition fragmentation chain transfer polymerization mediated by a phospholipid-modified trithiocarbonate. Temperature triggered the micellization of the PL-PNIPAM conjugate to form phosp...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 38(2022), 21 vom: 31. Mai, Seite 6612-6622
1. Verfasser: Li, Zhen (VerfasserIn)
Weitere Verfasser: Jiang, Yanfen, Zhao, Hanying, Liu, Li
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Drug Carriers Nanogels Phospholipids Polymers Doxorubicin 80168379AG Ribonuclease, Pancreatic EC 3.1.27.5
Beschreibung
Zusammenfassung:Thermoresponsive phospholipid-poly(N-isopropylacrylamide) (PL-PNIPAM) conjugates were synthesized via reversible addition fragmentation chain transfer polymerization mediated by a phospholipid-modified trithiocarbonate. Temperature triggered the micellization of the PL-PNIPAM conjugate to form phosphate group-decorated micelles in the aqueous solution. Driven by the chelation of phospholipids and Ca2+, the PL-PNIPAM conjugate and Ca2+ ions formed size-tunable nanoclusters at a temperature beyond the lower critical solution temperature. To fabricate cross-linked nanogels, NIPAM was copolymerized with N-succinimidyl acrylate (NSA) to obtain the PL-P(NIPAM-co-NSA) conjugate bearing pendent cross-linkable functionalities. Subsequently, the size-controllable nanogels containing disulfide linkages were generated at 37 °C by cross-linking the PL-P(NIPAM-co-NSA)/Ca2+ nanoclusters with cystamine through modulation of Ca2+ concentrations. These negatively charged nanogels demonstrate temperature/pH/reduction triple responsiveness. The nanogels can be efficiently loaded with doxorubicin (DOX) and proteins with various isoelectric points. The DOX-loaded nanogels exhibited a temperature/pH/reduction triple-responsive release profile. The immobilized RNase A, BSA, and GOx retained the protein bioactivity. The release of RNase A-loaded nanogels possesses a temperature-responsive profile. The immobilization of Lys and cytochrome C in nanogels inhibited protein bioactivity. However, the addition of NaCl triggered the recovery of bioactivity. These multistimuli-responsive nanogels can provide a versatile platform applicable in biotechnology and drug/protein delivery
Beschreibung:Date Completed 02.06.2022
Date Revised 03.08.2022
published: Print-Electronic
Citation Status MEDLINE
ISSN:1520-5827
DOI:10.1021/acs.langmuir.2c00464