Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance

Drug Delivery

Tian Lin¹  Weihong Guo¹  Hao Chen¹  Zhaoyu Chen¹  Guoxin Li¹  Jiang Yu¹  Hao Liu¹  Mingli Zhao¹  Yanfeng Hu¹  Tuanjie Li¹  Yanghee Woo²  Lizhi Deng³  Liming Zhang³ 

[1] Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR China;Department of Surgery, City of Hope National Medical Center, Duarte, CA, US;PCFM Lab and GDHPPC Laboratory, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, PR China;

关键词: Sericin;    pH-responsive;    micelle;    drug resistance;    doxorubicin;   

DOI  :  10.1080/10717544.2018.1469686

来源: publisher

【 摘 要 】

Drug resistance is the major challenge facing cancer chemotherapy and nanoscale delivery systems based on natural materials, such as sericin, are a promising means of overcoming drug resistance. Yet, no attempt of introducing synthetic poly(γ-benzyl-L-glutamate) (PBLG) onto sericin polypeptide to fabricate a facile biocompatible and biodegradable micelle has been tried. Here, we prepared a polypeptide-based amphiphilic polymer containing hydrophilic sericin polypeptide backbone and PBLG side chains via ring-opening polymerization (ROP) strategy. The introduction of PBLG side chains remarkably enhances the stability of sericin micelles in water. Meanwhile, the micelles exhibited a high loading capacity and pH-responsive release ability for antitumor drug doxorubicin (DOX), called sericin-PBLG-DOX. Owing to the excellent cell membrane penetration of sericin-PBLG, the cellular uptake of DOX when loaded into micelles was improved. Subsequently, sericin-PBLG-DOX was transferred into perinuclear lysosomes, where the release rate of DOX was accelerated. Compared to the same dose of DOX, sericin-PBLG-DOX could induce a more efficient anti-tumor effect both in vitro and in vivo, and these micelles have promise for future clinical applications in overcoming cancer drug resistance with good biosafety, enhanced cellular uptake, pH-triggered drug release, efficient anti-tumor effects, and minimized systemic toxicity.

【 授权许可】

CC BY