Synthetic enzyme inhibitor: a novel targeting ligand for nanotherapeutic drug delivery inhibiting tumor growth without systemic toxicity

Legumain-targeting improves liposomal NP-mediated drug delivery to solid tumors and eliminates systemic toxicity. PEG-liposomal NPs loaded with doxorubicin (Dox) were targeted to Legumain by conjugation with RR-11a, the synthetic enzyme inhibitor of Legumain. Hypoxia, a hallmark of solid tumors, induces over expression of Legumain on the surface of tumor cells. Thus, Legumain-targeting enhanced the specific homing of Dox-loaded NPs to solid tumors in vivo, resulting in complete inhibition of solid tumor growth without systemic toxicity (Black Arrows). In contrast, non-targeted NPs encapsulating Dox showed considerable non-specific accumulation in the liver, which diminished its anti-tumor effects and resulted in systemic toxicity (Gray Arrows).111