Transferrin-inspired vehicles based on pH-responsive coordination bond to combat multidrug-resistant breast cancer

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• 作者：Yu-Jing He^a ; ¹ ; Lei Xing^a ; ¹ ; Peng-Fei Cui^a ; Jia-Liang Zhang^a ; Yong Zhu^a ; Jian-Bin Qiao^a ; Jin-Yuan Lyu^a ; Mei Zhang^a ; Cheng-Qiong Luo^a ; Yu-Xin Zhou^a ; Na Lu^a ; ^{luna555@163.com" class="auth_mail" title="E-mail the corresponding author} ; Hu-Lin Jiang^a ; ^b ; ^c ; ^{jianghulin3@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Multidrug resistance ; pH-responsive ; Coordination bond ; Transferrin-inspired nanoparticles ; Doxorubicin
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：113
• 期：Complete
• 页码：266-278
• 全文大小：3041 K

文摘

A novel biomimetic drug delivery system (BDDS) inspired by the pH-dependent ferric ion-transport and release manner of transferrin (Tf) was developed for combating multidrug-resistant breast cancer. Tf-inspired carrier was synthesized by modifying bovine serum albumin (BSA) with histamine (HA) through amide reaction to provide superior specific coordination sites for ferric ion-drug complexes, and self-assembled into nanoparticles (NPs) induced by coordination bond. Tf-inspired NPs were prepared via environment-friendly method, and well redispersed in saline after lyophilization. When internalized into tumor cells by SPARC (secreted protein acidic and rich in cysteine) mediated endocytosis, Tf-inspired NPs bypassed and decreased the P-glycoprotein-mediated drug efflux and led to more effective treatment of multidrug-resistant breast cancer compared with free drugs both in vitro and in vivo due to the enhanced cellular uptake and rapid pH-responsive drug release. Moreover, Tf-inspired NPs exhibited good biocompatibility and low systemic toxicity. Thus, our results demonstrate that Tf-inspired NPs based on coordination bond represent as a smart drug delivery strategy to combat multidrug-resistant cancer and have great potential for clinical applications in cancer therapy.