Theranostic, pH-Responsive, Doxorubicin-Loaded Nanoparticles Inducing Active Targeting and Apoptosis for Advanced Gastric Cancer

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• 作者：Huanrong Ma ; Yuqing Liu ; Min Shi ; Xuebing Shao ; Wen Zhong ; Wangjun Liao ; Malcolm M. Q. Xing
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：December 14, 2015
• 年：2015
• 卷：16
• 期：12
• 页码：4022-4031
• 全文大小：628K
• ISSN：1526-4602

文摘

This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(尾-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F鈥揚-DOX). Confocal microscopy illustrated that F鈥揚-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F鈥揚-DOX. The better efficacy of F鈥揚-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F鈥揚-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F鈥揚-DOX could be a promising theranostic candidate for AGC treatment.