Calcium Phosphate-Reinforced Reduction-Sensitive Hyaluronic Acid Micelles for Delivering Paclitaxel in Cancer Therapy

For addressing the dilemma of in vivo stability and antitumor effects of micellar drugs, novel organic and inorganic hybridized nanoparticle, that is, hyaluronic acid-mineralized micelles, are designed to efficiently deliver paclitaxel (PTX). The resulting micelles exhibit excellent drug loading (30.6%) and entrapment efficiency (87.8%) for PTX with a small size (134.8 nm). Notably, the dual-sensitive release of PTX-loaded mineralized micelles is obtained in the conditions of 40 mM GSH and pH 5.0, whereas release is slow in the physiological environment. With favorable cell uptake, mineralized micelles show decent tumor accumulation, which corresponds to their significant targeting capacity from the observed real-time images. Compared with Taxol, PTX-loaded mineralized micelles show a lower half-maximal inhibitory concentration value (0.025 μg/mL), higher cell apoptosis rate (23.5%) in MDA-MB-231 cells, lower systemic toxicity to nude mice, and more potent in vivo tumor inhibition (1.57-times higher than that of Taxol (p < 0.05)).