Superparamagnetic Reduction/pH/Temperature Multistimuli-Responsive Nanoparticles for Targeted and Controlled Antitumor Drug Delivery

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• 作者：Jin Zeng ; Pengcheng Du ; Lei Liu ; Jiagen Li ; Kun Tian ; Xu Jia ; Xubo Zhao ; Peng Liu
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：December 7, 2015
• 年：2015
• 卷：12
• 期：12
• 页码：4188-4199
• 全文大小：680K
• ISSN：1543-8392

文摘

Multistimuli-responsive polymeric nanoparticles with core鈥搒hell 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 鈥済atekeeper鈥?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 鈥渢riggered release鈥?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.