Coating-Sheddable CD44-Targeted Poly(d,l-lactide-co-glycolide) Nanomedicines Fabricated by Using Photoclick-Crosslinkable Surfactant

Poly(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 degrees 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 mu g 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.