Coating‐Sheddable CD44‐Targeted Poly(d, l‐lactide‐co‐glycolide) Nanomedicines Fabricated by Using Photoclick‐Crosslinkable Surfactant. Issue 2 (23rd December 2019)

• Record Type: Journal Article
• Authors: Li, Shuai; Qiu, Min; Guo, Jiakun; Zhao, Xiaofei; Zhong, Zhiyuan; Deng, Chao
• Is Part Of: Advanced therapeutics. Volume 3:Issue 2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-12-23
• Subjects: cancer therapy -- click reaction -- nanomedicines -- stimuli‐sensitive -- targeted delivery; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.201900160
• Languages: English
• ISSNs: 2366-3987

Abstract

Abstract: 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 °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. Abstract : Coating‐sheddable CD44‐targeted poly(d, l ‐lactide‐ co ‐glycolide) nanoparticles are developed using a photoclick‐crosslinkable hyaluronic‐ g ‐tetrazole conjugate as a surfactant (X‐PHS@NPs) for targeted delivery of docetaxel (DTX) to breast tumors. X‐PHS@NPs have several unique features including easy fabrication, high stability, CD44‐targetability, superb tumor penetration, as well as reduction‐triggered drug release; and DTX‐loaded X‐PHS@NPs demonstrate more effective inhibition of MCF‐7 human breast tumor xenografts than the free drug.