Acoustic triggered nanobomb for US imaging guided sonodynamic therapy and activating antitumor immunity

Abstract

We fabricated an ultrasound activated ‘nanobomb’ as a noninvasive and targeted physical therapeutic strategy for sonodynamic therapy and priming cancer immunotherapy. This ‘nanobomb’ was rationally designed via the encapsulation of indocyanine green (ICG) and perfluoropentane (PFP) into cRGD peptide-functionalized nano-liposome. The resulting Lip-ICG-PFP-cRGD nanoparticle linked with cRGD peptide could actively targeted ID8 and TC-1 cells and elicits ROS-mediated apoptosis after triggered by low-intensity focused ultrasound (LIFU). Moreover, the phase change of PFP (from droplets to microbubbles) under LIFU irradiation can produce a large number of microbubbles, which act as intra-tumoral bomber and can detonate explode tumor cells by acoustic cavitation effect. Instant necrosis of tumor cells further induces the release of biologically active damage-associated molecular patterns (DAMPs) to facilitate antitumor immunity. More important, the ‘nanobomb’ in combination with anti-PD-1checkpoint blockade therapy can significantly improve the antitumor efficacy in a subcutaneous model. In addition, the liposomes may also be used as an imaging probe for ultrasound (US) imaging after being irradiated with LIFU. In summary, the US imaging-guided, LIFU activated ROS production and explosion ‘nanobomb’ might significantly improve the antitumor efficacy and overcome drug resistance through combination of SDT and immunotherapy, we believe that this is a promising approach for targeted therapy of solid tumor including ovarian cancer.