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Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery

Qiu, Min, Ouyang, Jia, Sun, Huanli, Meng, Fenghua, Cheng, Ru, Zhang, Jian, Cheng, Liang, Lan, Qing, Deng, Chao, Zhong, Zhiyuan
ACS applied materials & interfaces 2017 v.9 no.33 pp. 27587-27595
adverse effects, antineoplastic activity, antineoplastic agents, biodegradability, chloroform, composite polymers, ethylene glycol, growth retardation, hydrophobicity, in vitro studies, inhibitory concentration 50, lysosomes, melanoma, methylene chloride, micelles, nanocarriers, phosphates, polyethylene glycol, polymerization, polypeptides, solubility, solvents, survival rate
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(α-aminopalmitic acid) (PEG-b-PAPA) block copolymer could be easily prepared with tailored Mₙ through ring-opening polymerization of α-aminopalmitic acid N-carboxyanhydride (APA-NCA). Interestingly, PEG-b-PAPA copolymers exhibited superb solubility in common organic solvents (including CHCl₃, CH₂Cl₂, 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 μg 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.