Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 9, Pages 7811-7820Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b18887
Keywords
reduction sensitivity; core cross-linked nanoparticles; polyphosphoesters; Michael addition polymerization; folic acid
Funding
- National Natural Science Foundation of China [21374066]
- Major Program of the Natural Science Project of Jiangsu Higher Education Institutions [15KJA150007]
- Natural Science Foundation of Jiangsu Province [BK20171212]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
- Soochow-Waterloo University Joint Project for Nanotechnology from Suzhou Industrial Park
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To improve the therapeutic efficacy and circulation stability in vivo, we synthesized a new kind of drug delivery carrier based on folic acid conjugated polyphosphoester via the combined reactions of Michael addition polymerization and esterification. The produced amphiphilic polymer, abbreviated as P(EAEP-AP)-LA-FA, could self-assemble into nanoparticles (NPs) with core-shell structure in water and reversible core cross-linked by lipoyl groups. Using the core cross-linked FA-conjugated nano particles (CCL-FA NPs) to encapsulate hydrophobic anticancer drug doxorubicin (DOX), we studied the stability of NPs, in vitro drug release, cellular uptake, and targeting intracellular release nanoparticles (UCL-FA NPs) and core cross-linked nanoparticles without FA conjugation (CCL NPs). The results showed that under the condition of pH 7.4, the DOX-loaded CCL-FA NPs could maintain stable over 72 h, and only a little DOX release (similar to 15%) was observed. However, under the reductive condition (pH 7.4 containing 10 mM GSH), the disulfide-cross-linked core would be broken up and resulted in 90% of DOX release at the same incubation period. The study of methyl thiazolyl tetrazolium (MTT) assay indicated that the DOX-loaded CCL-FA NPs exhibited higher cytotoxicity (IC50: 0.33 mg L-1) against HeLa cells than the DOX-loaded CCL NPs without FA. These results indicate that the core cross-linked FA-conjugated nanoparticles have unique stability and targetability.
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