Solvent mediated morphology of ZrZnS nanocrystals for synergistic surface-functionalization with gefitinib and miR146 for cancer treatment

Synthesized ZrZnS (ZZS) nanocrystals (NCs) demonstrate solvent-mediated morphological control and changes. In ethanol, ZZS NCs adopt well-defined cuboidal structures with uniform facets, whereas a dichloromethane-isopropanol (DCM:IPA, 1:1 v/v) system promotes the formation of irregular hexagonal nanostructures, revealing solvent-ratio-dependent anisotropic growth under dark incubation. The positively charged ZZS NCs (confirmed by zeta potential, ζ) were further functionalized with an anti-cancer drug (gefitinib/GFT, a tyrosine kinase inhibitor) and miR-146, a dual-functional miRNA regulating immune response and cancer progression. The resulting GFT-miR146@ZZS NCs exhibited efficient cellular uptake in LLC malignant cells. In vitro and in vivo evaluations demonstrated significant inhibition (~ 90%) of lung cancer cell proliferation and tumor repolarization via modulation of tumor-associated macrophages (TAMs). Tumor microenvironment (TME) suppresses M2-phenotype TAMs (pro-tumorigenic) and promotes repolarization to M1-phenotype TAMs (anti-tumorigenic). This synergistic approach highlights the potential of ZZS NCs as a versatile platform for combinatorial cancer therapy.