Hyaluronic acid mediated Fe₃O₄ nanocubes reversing the EMT through targeted cancer stem cell

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Hepatocellular carcinoma (HCC) presents significant global health challenges due to high mortality, recurrence, and metastasis rates.
• Cancer stem cells (CSCs) are crucial drivers of HCC recurrence, treatment resistance, and metastasis, necessitating targeted therapeutic strategies.
• Developing innovative drug delivery systems is critical for effective HCC treatment.

Purpose of the Study:

• To engineer composite magnetic nanocubes for targeted delivery to HCC stem cells.
• To investigate the therapeutic potential of these nanocubes loaded with LDN193189 for inhibiting HCC progression.
• To evaluate the dual-targeting efficacy of the developed system.

Main Methods:

• Fabrication of polyethyleneimine (PEI) and hyaluronic acid (HA)-modified Fe3O4 magnetic nanocubes using a high-temperature thermal breakdown approach.
• Utilizing the HA-CD44 receptor-ligand interaction for specific targeting of HCC stem cells.
• Loading the small molecule LDN193189 to inhibit stemness genes (OCT4, Nanog) and assessing the impact on epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, N-cadherin).

Main Results:

• The Fe3O4 nanocubes effectively recognized and targeted HCC stem cells via HA-CD44 binding.
• LDN193189-loaded nanocubes significantly suppressed HCC cell proliferation and migration.
• Dual magnetic and receptor-mediated targeting enhanced the uptake of the drug delivery system.
• Regulation of EMT markers indicated suppression of tumor invasiveness.

Conclusions:

• The developed HA-modified Fe3O4 magnetic nanocubes represent a promising targeted drug delivery platform for HCC.
• This approach effectively targets cancer stem cells and inhibits key processes driving tumor progression.
• The findings suggest a potential new therapeutic strategy for hepatocellular carcinoma treatment.