Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance.
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.
['Guo|Weihong|W|', 'Deng|Lizhi|L|', 'Yu|Jiang|J|', 'Chen|Zhaoyu|Z|', 'Woo|Yanghee|Y|', 'Liu|Hao|H|', 'Li|Tuanjie|T|', 'Lin|Tian|T|', 'Chen|Hao|H|', 'Zhao|Mingli|M|', 'Zhang|Liming|L|', 'Li|Guoxin|G|', 'Hu|Yanfeng|Y|']
D000818:Animals D000970:Antineoplastic Agents D012831:Bombyx D045744:Cell Line, Tumor D004317:Doxorubicin D004337:Drug Carriers D016503:Drug Delivery Systems D065546:Drug Liberation D019008:Drug Resistance, Neoplasm D056945:Hep G2 Cells D006801:Humans D006863:Hydrogen-Ion Concentration D057927:Hydrophobic and Hydrophilic Interactions D061986:MCF-7 Cells D008297:Male D008823:Micelles D053758:Nanoparticles D009369:Neoplasms D010455:Peptides D011099:Polyglutamic Acid D011108:Polymers D051381:Rats D017207:Rats, Sprague-Dawley D047030:Sericins
Sericin doxorubicin drug resistance micelle pH-responsive