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  • Title: Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy.
    Author: Xiang J, Wu B, Zhou Z, Hu S, Piao Y, Zhou Q, Wang G, Tang J, Liu X, Shen Y.
    Journal: Sci China Life Sci; 2018 Apr; 61(4):436-447. PubMed ID: 29572777.
    Abstract:
    Paclitaxel (PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly (ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate (PEITC), a hydrophobic anticancer agent under clinical study. The amphiphilic conjugate (PEG-Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined micelles whose core was composed of phenyl groups and thiourea groups binding PTX via π-π stacking and hydrogen bonding. Compared with the PTX-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEGPDLLA/ PTX) micelles in clinical use, PTX-loaded PEG-Gx-PEITC third-generation (PEG-G3-PEITC/PTX) micelles showed slowed blood clearance, enhanced tumor accumulation, and thus much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug delivery system for PTX in the treatment of breast cancer.
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