Small PLGA nanocapsules Co-encapsulating copper sulfide nanodots and fluorocarbon compound for photoacoustic imaging-guided HIFU synergistic therapy

High intensity focused ultrasound (HIFU), as a promising and minimally invasive therapeutic modality against various solid tumors, has received considerable attention in the biomedical field. However, both the accuracy and efficacy of this technique are currently unsatisfactory. Herein, a nanometer-sized organic/inorganic hybrid enhancement agent for photoacoustic imaging (PAI)-guided HIFU therapy was designed and fabricated by concurrently encapsulating both Cu(2−x)S nanodots (NDs) and perfluorooctyl bromide (PFOB) into a poly(lactic-co-glycolic acid) PLGA nanocapsule (denoted CPPNs). These nanocapsules assumed a unique core/satellite/shell sandwich structure, and combined the merits of small and uniform particle size (about 120 nm), favorable biosafety, and multifunctional theranostic ability into one system. The high performance of Cu(2−x)S NDs in the absorption and conversion of near infrared laser confers high PAI contrast capability to the CPPNs, by which the location of the CPPNs within a tumor can be monitored successfully under PAI. Furthermore, our in vitro and in vivo results confirmed that the encapsulated PFOB in CPPNs increased the cavitation effect and thus enhanced the ablation efficacy under HIFU exposure. CPPNs show great potential as an efficient and powerful theranostic agent for future PAI-guided HIFU synergistic therapy.