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 MoS2nanosheets ([email protected]2-PEG NSs) as a feasible approach to enhance cellular uptake.[email protected]2-PEG NSs can maintain good dispersion stability in cell culture medium and effectively protect MoS2NSs from oxidation in ambient aqueous conditions. Competitive adsorption experiments indicate that transferrin was more prone to bind MoS2NSs than bovine serum albumin (BSA). It is noteworthy that single HepG2 cell uptake of[email protected]2-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[email protected]2-PEG and MoS2-PEG showed narrower distribution, indicating homogeneous uptake in the single HepG2 cells. Over 5% of HepG2 cells presented uptake of the[email protected]2-PEG over 1.2 fg of Mo, about three-fold that of[email protected]2-PEG (0.4 fg of Mo). Overall, this work suggests that Tf coating enhances the cellular uptake of MoS2NSs and is a promising strategy for improving the intracellular uptake efficiency of cancer cells.Keywords:bi-functionalization;[email protected]2-PEG nanosheets;HepG2 cellular uptake