机构:[1]Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China[2]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
Poly(ethylene glycol)-b-polypeptide block copolymer micelles, with excellent safety, are one of the most clinically studied nanocarriers for anticancer drug delivery. Notably, self-assembled nanosystems based on hydrophobic polypeptides showing typically a low drug loading and burst drug release are limited to preclinical studies. Here, we report that poly(ethylene glycol)-b-poly(alpha-aminopalmitic acid) (PEG-b-PAPA) block copolymer could be easily prepared with tailored M-n through ring-opening polymerization of alpha-aminopalmitic acid N-carboxyanhydride (APA-NCA). Interestingly, PEG-b-PAPA copolymers exhibited superb solubility in common organic solvents (including CHCl3, CH2C6 and THF), while stable nanomicelles were formed in phosphate buffer, with a small size of 59 nm and a low critical micelle concentration of 2.38 mg/L. These polylipopeptide micelles (Lipep-Ms) allowed facile loading of a potent anticancer drug, docetaxel (DTX), likely due to the existence of a strong interaction between the lipophilic drug and polylipopeptide in the core. Notably, cRGD-peptide-functionalized Lipep-Ms (cRGD-Lipep-Ms) were also obtained with similar biophysical characteristics. The in vitro studies showed efficient cellular uptake of DTX-loaded cRGD-Lipep-Ms by B16F10 cells and fast intracellular drug release due to the enzymatic degradation of PAPA blocks in endo/lysosome, leading to a pronounced anticancer effect (IC50 = 0.15 mu g DTX equiv/mL). The in vivo therapy studies showed that DTX-cRGD-Lipep-Ms exhibited superior tumor growth inhibition of B16F10 melanoma, improved survival rate, and little side effects as compared to free DTX. These polylipopeptide micelles appear as a promising and robust nanoplatform for anticancer drug delivery.
基金:
This work was supported by the National Natural Science
Foundation of China (NSFC 51473110 and 51633005).
第一作者机构:[1]Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China
通讯作者:
通讯机构:[1]Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China
推荐引用方式(GB/T 7714):
Qiu Min,Ouyang Jia,Sun Huanli,et al.Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery[J].ACS APPLIED MATERIALS & INTERFACES.2017,9(33):27587-27595.doi:10.1021/acsami.7b10533.
APA:
Qiu, Min,Ouyang, Jia,Sun, Huanli,Meng, Fenghua,Cheng, Ru...&Zhong, Zhiyuan.(2017).Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery.ACS APPLIED MATERIALS & INTERFACES,9,(33)
MLA:
Qiu, Min,et al."Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery".ACS APPLIED MATERIALS & INTERFACES 9..33(2017):27587-27595