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

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 (VD ₃ ). Herein, we designed a series of self-assembled micelles. The conjugate (HA-VD) of VD ₃ with hyaluronic acid (HA) actively targeting breast cancer can efficiently delivery doxorubicin (DOX). The HA-VD conjugate was successfully synthesized, which was confirmed using ¹ H nuclear magnetic resonance (NMR) and Fourier transform infrared (FITR). Preliminary studies of its physical and chemical properties indicated that VD ₃ 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 IC ₅₀ 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, VD ₃ 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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