Dual-targeted enzyme-sensitive hyaluronic acid nanogels loading paclitaxel for the therapy of breast cancer

In this study, a CD44 and biotin receptors dual-targeted enzyme-sensitive hyaluronic acid nanogel loading paclitaxel (PTX/Bio-NG) for targeting breast cancer was constructed. Spherical nanogels with a mean particle size of 149.1 +/- 1.6 nm, higher entrapment efficiency (90.17 +/- 0.52 %) and drug loading (15.28 +/- 0.10 %) were obtained. PTX/Bio-NG quickly released drugs under the catalysis of hyaluronidase and/or lipase. Cell studies revealed that the uptake of Bio-NG by 4T1 cells was mediated by CD44 receptor and Bio-specific receptor. Compared with PTX-loaded biotin-free NG (PTX/NG), PTX/Bio-NG had higher cytotoxicity against breast cancer cells (4T1 cells). The rats pharmacokinetic profile indicated higher AUC(0-t) but lower clearance rates of PTX/NG (6.24 times and 15.96 %, respectively) and PTX/Bio-NG (6.66 times and 14.89 %, respectively) than control group (Taxol). In vivo studies showed that PTX/Bio-NG possessed excellent therapeutic efficacy in 4T1 tumorbearing Balb/c mice, which suggest that PTX/Bio-NG could be an excellent candidate for the treatment of breast cancer.