Abstract
AbstractPoly(d,l‐lactide‐co‐glycolide) (PLGA)‐based nanotherapeutics are intensively employed for the treatment of various diseases, though they frequently suffer from stability, selectivity, and drug release problems. Here, a facile fabrication of coating‐sheddable CD44‐targeted PLGA nanoparticles using photoclick‐crosslinkable hyaluronic acid‐graft‐tetrazole (HA‐g‐Tet) as a surfactant followed by photoclick reaction with l‐cystine dimethacrylamide (MA‐Cys‐MA) (X‐PHS@NPs) for targeted delivery of docetaxel (DTX) to breast tumors in vivo is reported. X‐PHS@NPs exhibit strong blue fluorescence and a size of 109 nm. DTX‐loaded X‐PHS@NPs (DTX‐X‐PHS@NPs), while stable at physiological conditions (pH 7.4, 37 °C), release about 76.6% DTX under 10 m glutathione conditions. DTX‐X‐PHS@NPs are potent toward CD44‐overexpressing MCF‐7 human breast cancer cells with a low IC50 of 0.27 µg mL−1. Interestingly, X‐PHS@NPs reveal excellent tumor penetration ability and DTX‐X‐PHS@NPs induce significantly more effective inhibition of MCF‐7 human breast tumors in nude mice than free DTX. These coating‐sheddable CD44‐targeted PLGA nanoparticles provide an interesting platform for cancer chemotherapy.
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