Protein corona-guided tumor targeting therapy via the surface modulation of low molecular weight PEG

The discovery of protein corona (PC) formed on the surface of nanomaterials has promoted research on PC regulation to guide the biological behavior of nanomaterials in vivo. Different from changing the size, shape, and surface charge of nanoparticles, we propose to control the nature of PC by adjusting the molecular weight of low molecular weight polyethylene glycol (LMW PEG, not more than 1000 Da) on the surface of the particles. After excluding the influence of physicochemical factors of PEGylated gold nanoparticles (GNPs), different proteins on the surface of PEGylated GNPs were separated and identified after incubation with human plasma. It is noted that GNP-550 bearing PEG chains of 550 Da absorbed more transferrin responsible for tumor targeting than the other two particles, i.e., GNP-350 and GNP-1000. To validate our speculation, doxorubicin (Dox) was inserted between GNPs and PEGs to explore the cellular and animal studies of Dox-conjugated GNPs. Interestingly, Dox-containing Conj-550 also showed the highest intracellular uptake, cytotoxicity, and apoptosis against HepG2 cells, as well as the best tumor targeting effect and antitumor efficacy in Heps-bearing mice. This protein corona-guided tumor targeting therapy by transferrin provides a new perspective on the function modulation of nanomedicine via LMW PEGs.