Redox-Sensitive and Bone-Targeting Self-Assembled Polymeric Nanomicelles Based on Hyaluronic Acid for Bone Metastasis Treatment.

Treatment methods for bone metastasis often face difficulties because of inadequate blood flow and poor drug absorption in bone tissue. Addressing these challenges, a multifunctional targeting nanomicelle was developed utilizing hyaluronic acid (HA) as the base polymer, functionalized with sodium alendronate (ALN) as a bone-targeting ligand and an antibone resorption agent (ALN-HA). To impart a redox-responsive property, disulfide bonds were integrated into the nanomicelle structure using cystamine (CYS). Finally, vitamin E succinate (VES) was used as the hydrophobic tail of the prepared nanomicelles (ALN-HA-CYS-VES), which have been loaded with curcumin (CUR), as an antitumor agent. The chemical structure of the synthesized polymers was evaluated and confirmed using FTIR and NMR. The mean diameter of prepared nanomicelles was determined as 148.2 ± 2.3 nm, with a narrow distribution size (PDI = 0.169) and critical micelle concentration (CMC) of 49.2 ± 1.8  μg/mL. The drug loading and encapsulation efficiency of CUR were measured as 4.68% and 49.1%, respectively. The drug release profile revealed that approximately 70% of CUR was released in a tumor-like environment, compared with about 44.7% ± 0.9% under normal tissue conditions. Hydroxyapatite assay confirmed the high affinity of ALN-HA-CYS-VES for bone mineral matrix (74.20%), whereas this value is only 15.45% for HA-CYS-VES. These results indicate that the ALN-modified HA-based nanomicelles could emerge as a promising platform for the delivery of anticancer drugs in the treatment of bone metastasis.