Bi-Functionalized Transferrin@MoS₂-PEG Nanosheets for Improving Cellular Uptake in HepG2 Cells

Pre-coating with a protein corona on the surface of nanomaterials (NMs) is an important strategy for reducing non-specific serum protein absorption while maintaining targeting specificity. Here, we present lipoic acid-terminated polyethylene glycol and transferrin bi-functionalized MoS₂ nanosheets (Tf@MoS₂-PEG NSs) as a feasible approach to enhance cellular uptake. Tf@MoS₂-PEG NSs can maintain good dispersion stability in cell culture medium and effectively protect MoS₂ NSs from oxidation in ambient aqueous conditions. Competitive adsorption experiments indicate that transferrin was more prone to bind MoS₂ NSs than bovine serum albumin (BSA). It is noteworthy that single HepG2 cell uptake of Tf@MoS₂-PEG presented a heterogeneous distribution pattern, and the cellular uptake amount spanned a broader range (from 0.4 fg to 2.4 fg). Comparatively, the intracellular Mo masses in HepG2 cells treated with BSA@MoS₂-PEG and MoS₂-PEG showed narrower distribution, indicating homogeneous uptake in the single HepG2 cells. Over 5% of HepG2 cells presented uptake of the Tf@MoS₂-PEG over 1.2 fg of Mo, about three-fold that of BSA@MoS₂-PEG (0.4 fg of Mo). Overall, this work suggests that Tf coating enhances the cellular uptake of MoS₂ NSs and is a promising strategy for improving the intracellular uptake efficiency of cancer cells.