Prolonged blood circulation outperforms active targeting for nanocarriers-mediated enhanced hepatocellular carcinoma therapy in vivo.

Successful hepatocellular carcinoma (HCC) therapy in vivo remains a significant challenge due to the down-regulated expression of the receptors on the surface of tumor cells for compromised active targeting efficiency and cellular uptake of nanoparticles (NPs)-based drug delivery systems (DDSs) and "accelerated blood clearance" and premature unpackaging of NPs in vivo induced by the poly(ethylene glycol)ylation (PEGylation). Inspired by the repeatedly highlighted prolonged blood circulation property of RBCm-camouflaged NPs, we hypothesis that the prolonged blood circulation property resulting from RBCm coating outperforms the active targeting mechanisms of various targeting ligands for enhanced HCC therapy in vivo. Clarification of this hypothesis is therefore of great significance and urgency to break the afore mentioned bottlenecks that hamper the efficient HCC treatment in vivo.