Improvement of drug penetration in solid tumors by vascular disruption with acoustic nanodroplet vaporization

Acoustic droplet vaporization (ADV) provides chemical and physical effects due to the mechanical force and drug releasing. Although nanodroplets can passive penetrate and deliver drugs into tumor tissue via the enhanced permeability and retention (EPR) effect, various aspects of the tumor microenvironment still restrict this process. Therefore, our study applied vascular disruption induced by ADV to overcome the limitations of the EPR effect to allow drug penetration into extensive regions. The dorsal skinfold window chamber model and acousto-optical integrated system were applied to evaluate the intravital penetration of DiI-labeled liposomes. The cumulative penetration areas and extravascular fluorescence ratios of the ADV group were 3.46 fold and 1.7 fold, respectively, higher than that of the EPR group at 180 min. Histology images demonstrated that ADV can improve the DiI-labeled liposomes penetration at the locations of intratumoral tissue damage and vascular disruption. This proposed strategy might improve the drug accumulation in some tumors with poorly vascular permeability and deliver drugs into tumor hypoxia regions.