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

Abstract

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.

• Authors: Weihong Guo, Lizhi Deng, Jiang Yu, Zhaoyu Chen, Yanghee Woo, Hao Liu, Tuanjie Li, Tian Lin, Hao Chen, Mingli Zhao, Liming Zhang, Guoxin Li, Yanfeng Hu
• Journal: Drug delivery (Drug Deliv) Vol. 25 Issue 1 Pg. 1103-1116 (Nov 2018) ISSN: 1521-0464 [Electronic] England
• PMID: 29742945 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Micelles
• Peptides
• Polymers
• Sericins
• poly-gamma-benzyl-L-glutamate
• Polyglutamic Acid
• Doxorubicin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Bombyx
• Cell Line, Tumor
• Doxorubicin (pharmacology)
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Drug Liberation
• Drug Resistance, Neoplasm (drug effects)
• Hep G2 Cells
• Humans
• Hydrogen-Ion Concentration
• Hydrophobic and Hydrophilic Interactions
• MCF-7 Cells
• Male
• Micelles
• Nanoparticles (chemistry)
• Neoplasms (drug therapy)
• Peptides (chemistry)
• Polyglutamic Acid (analogs & derivatives, chemistry)
• Polymers (chemistry)
• Rats
• Rats, Sprague-Dawley
• Sericins (pharmacology)