Hyaluronic acid and cholecalciferol conjugate based nanomicelles: Synthesis, characterization, and cytotoxicity against MCF-7 breast cancer cells

Abstract

Recently, growing and conclusive evidences showed the particularly close ties between the vitamin D (VD) and breast cancer (BC). However, few researches were focused on the delivery system against breast cancer which based on cholecalciferol (VD3). Herein, we designed a series of self-assembled micelles. The conjugate (HA-VD) of VD3 with hyaluronic acid (HA) actively targeting breast cancer can efficiently delivery doxorubicin (DOX). The HA-VD conjugate was successfully synthesized, which was confirmed using 1H nuclear magnetic resonance (NMR) and Fourier transform infrared (FITR). Preliminary studies of its physical and chemical properties indicated that VD3 was successfully grafted with the HA (HAVD). When the molar ratio was 1:2 and the degree of substitution (DS) was 18.6%, the minimum critical micelle concentration (CMC) value was 0.0137 mg/mL. For DOX-loaded HAVD micelles (DOX/HAVD), the drug loading (DL) was 6.2% and drug encapsulation efficiency (EE) was 79.5%. The DOX/HAVD micelles remain stable in serum for 48 h. The in vitro release rate of DOX decreased after encapsulating compared with that without HAVD encapsulation. The decrease with IC50 of DOX/HAVD micelle was significantly stronger than that of free DOX (p < 0.05) and blank micelles (p < 0.01). At 50% cell inhibition rate, VD3 and DOX acted synergistically on BC cells. Hence, the HAVD micelles can significantly improve the therapeutic effect of DOX against BC cells. In a word, the DOX/HAVD micelles have great potential in treating breast cancer.