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

Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world with a high rate of recurrence and metastasis. Therefore, the most pressing issue today is the development of new drugs, diagnostic and therapeutic approaches for effective cancer treatment. Cancer stem cells (CSCs) play a pivotal role in tumor recurrence, tumor resistance, and tumor metastasis, which provides a new perspective on the development of liver cancer. In the study, a high-temperature thermal breakdown approach was used to create composite magnetic nanocubes modified by polyethyleneimine (PEI) and hyaluronic acid (HA). The Fe3O4 nanocubes can recognize HCC stem cells via receptor-ligand binding of HA and CD44 (HA receptor). While loading a small molecule LDN193189 inhibited the expression of stemness-related genes OCT4 and Nanog. More crucially, the Fe3O4 nanocubes significantly suppressed HCC cell proliferation and migration by regulating the expression of epithelial-mesenchymal transition (EMT) process markers E-cadherin, Vimentin, and N-cadherin. Dual targeting using magnetic and receptor-mediated targeting improved the uptake of the drug delivery system. Our findings imply that the medication delivery method might be a potential therapeutic strategy for HCC.