Preparation of hyaluronic acid-loaded Harmine polymeric micelles and in vitro effect anti-breast cancer

Aims: To prepare hyaluronic acid-loaded Harmine polymeric micelles with CD44 targeting properties and to investigate their anti-breast cancer effects in vitro.Methods: The carboxyl group on hyaluronic acid is coupled to the amino group on 3,5-bis(trifluoromethyl)benzyl-amine by an amidation reaction. And the polymeric micelles self-assemble to encapsulate the Harmine in a hydrophobic core, characterized the polymer micelles by IR, 19F-NMR, Malvern particle sizing, release, hemo-lysis, and other experiments. Used CD44-positive MDA-MB-231 cells and CD44-negative MCF-7 cells as tumor models. The effect of polymer micelles on breast cancer cells in vitro by cytotoxicity assay, confocal, and flow cytometry.Results: The prepared polymer micelles had a uniform particle size of about 200 nm, good dispersion, PDI < 0.3, encapsulation rate up to 87%, drug loading of 4.12 +/- 0.03%, and negative charge. Hyaluronidase has a good enzymatic effect on polymeric micelles, with a hemolysis rate of less than 1%. It showed some dose-dependent toxicity to both MDA-MB-231 and MCF-7, with increased uptake of polymer micelles by CD44-positive MDA-MB-231 compared to CD44-negative MCF-7 cells and significant effects of polymer micelles on apoptosis and cycling in both cell types. These results suggest that the hyaluronic acid-loaded Harmine polymer micelles designed in this study are effective in killing breast cancer cells while at the same time reducing the toxicity of Harmine and improving its slow-release targeting.

Automated summary

In this study, hyaluronic acid-loaded Harmine polymeric micelles with CD44 targeting properties were prepared, and their anti-breast cancer effects were investigated in vitro. The prepared micelles had a uniform particle size of about 200 nm, good dispersion, high encapsulation rate, and drug loading. They showed dose-dependent toxicity to both CD44-positive MDA-MB-231 and CD44-negative MCF-7 cells, with increased uptake by MDA-MB-231 cells and significant effects on apoptosis and cell cycling in both cell types.