期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 12, 页码 4188-4199出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00342
关键词
polymer nanoparticles; superparamagnetic; multiresponsive; antitumor drug delivery; distillation precipitation polymerization; controlled release
资金
- National Nature Science Foundation of China [20904017]
- Program for New Century Excellent Talents in University of Ministry of Education of China [NCET-09-0441]
Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a gatekeeper on the surface via two-stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)-cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the triggered release of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy.
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