Abstract
CD44 play a pivotal role in tumor progression and metastasis. Targeting CD44 expressing cells using hyaluronic acid (HA) is a promising approach in the treatment of many types of tumors. Here, CD44-targeted conjugate was introduced by hyaluronic acid-deoxycholic acid (HA-DOCA) through the connection of the ester bond. Hydrophilic drug Gemcitabine (GEM) and hydrophobic DOCA are linked by the amide linkage. The DOCA-GEM was mixed with HA-DOCA to form mixed micelles (MMs) with low critical micelle concentration. Dynamic laser light scattering and transmission electron microscope measurements revealed that HA-DOCA/DOCA-GEM MMs displayed sphericity, with an average diameter of 149 ± 3 nm, and negative zeta potential. Hemolysis and cytotoxicity studies confirmed the safety of the HA-DOCA conjugate. The in vitro drug release was investigated, demonstrating that the intracellular-mimicking microenvironment could accelerated the GEM release of the HA-DOCA/DOCA-GEM MMs. The HA-DOCA/DOCA-GEM MMs showed higher cellular uptake efficiency by MCF-7 cells according to confocal laser scanning microscopy and flow cytometry, therefore achieving much stronger anticancer efficacy than free GEM and DOCA-GEM micelles. Our results suggest that HA-DOCA/DOCA-GEM MMs might be a potential candidate for cancer therapy.
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