Journal of Drug Delivery Science and Technology, vol.117, 2026 (SCI-Expanded, Scopus)
The prevalence of cancer is on the rise on a global scale, and lung cancer represents one of the most common types of cancer worldwide that leads to high cancer-related deaths. Over the past decade, nanotechnology has made tremendous progress in cancer treatment. Moreover, combination therapy, including chemotherapy and gene therapy, has turned out to be a promising strategy that could enhance therapeutic efficacy in the treatment of lung adenocarcinoma. The tumor-suppressive miRNA-424-3p has demonstrated to significantly downregulate galectin-3 (Gal3) which is an anti-apoptotic protein and highly expressed in A549 cells. This has been shown to promote apoptosis, decrease proliferation, and increase sensitivity to the chemotherapeutic drug doxorubicin (Dox). However, miRNA-424-3p-based combination therapies with Dox have not yet been reported. Since dendritic mesoporous silica nanoparticles (DMSNs) have the potential to act as carriers for nucleic acids and drugs simultaneously, in this study we have successfully introduced for the first time anti-Gal3 functionalized DMSNs for the co-delivery of miRNA-424-3p and Dox protected with a layer-by-layer polyethyleneimine and poly-L-lysine coating. Whereas there is no or minimal Dox and miRNA release under neutral pH from the nanoparticles, conversely, a significant delivery of Dox and miRNA is seen in lysosomal extract medium. The effects of the co-delivery system, i.e. miRNA-424-3p and Dox, on A549 cells is evaluated by analyzing cell proliferation, cellular uptake, cell apoptosis assay, and the expression of related proteins and genes. The results demonstrate that miRNA-424-3p effectively transfected into A549 lung cancer cells, dramatically reducing the expression of Gal3 at the protein level. Forward transfection of the cell line with the DMSN loaded with miRNA-424-3p and Dox causes both a decrease in cell viability and an increase in apoptosis induction. Our data shows that the designed DMSN has a good performance as a combined drug and gene delivery system for cancer therapy.