Shaping the "hot" immunogenic tumor microenvironment by nanoparticles co-delivering oncolytic peptide and TGF-β1 siRNA for boosting checkpoint blockade therapy.

Induction of potent immune responses toward tumors remains challenging in cancer immunotherapy, in which it only showed benefits in a minority of patients with "hot" tumors, which possess pre-existing effector immune cells within the tumor. In this study, we proposed a nanoparticle-based strategy to fire up the "cold" tumor by upregulating the components associated with T and NK cell recruitment and activation and suppressing TGF-β1 secretion by tumor cells. Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).