Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma

A transferrin targeted core-shell nanomedicine encapsulating two clinically used drugs, sorafenib and doxorubicin, against hepatocellular carcinoma (HCC) was in silico designed and developed. The multikinase inhibitor, sorafenib loaded protein nano-shell inhibits cell proliferation whereas the DNA intercalating drug, doxorubicin loaded polymer nano-core exerts cytotoxic stress, leading to ~ 93% synergistic cytotoxicity in 2D and 3D cultures of HCC. This in silico optimized nanomedicine shows great potential for the simultaneous delivery of hydrophobic (sorafenib), and hydrophilic drug (doxorubicin) to inhibit key cancer signaling events together with cytotoxic stress.165