RESUMO
PURPOSE: Photodynamic therapy (PDT), sonodynamic therapy (SDT), and oxaliplatin (OXP) can induce immunogenic cell death (ICD) following damage-associated molecular patterns (DAMPs) exposure or release and can be united via the use of nanoplatforms to deliver drugs that can impart anti-tumor effects. The aim of this study was to develop phase-transition nanoparticles (OI_NPs) loaded with perfluoropentane (PFP), indocyanine green (ICG), and oxaliplatin (OXP), to augment anti-tumor efficacy and the immunological effects of chemotherapy, photodynamic therapy and sonodynamic therapy (PSDT). METHODS: OI_NPs were fabricated by a double emulsion method and a range of physicochemical and dual-modal imaging features were characterized. Confocal microscopy and flow cytometry were used to determine the cellular uptake of OI_NPs by ID8 cells. The viability and apoptotic rate of ID8 cells were investigated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and ï¬ow cytometry. Flow cytometry, Western blotting, and luminometric assays were then used to investigate the exposure or release of crucial DAMPs such as calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine-5'-triphosphate (ATP). Tumor rechallenge experiments were then used to investigate whether treated ID8 cells underwent ICD. Finally, cytotoxic T lymphocyte (CTL) activity was determined by a lactate dehydrogenase (LDH) assay. RESULTS: Spherical OI_NPs were able to carry OXP, ICG and PFP and were successfully internalized by ID8 cells. The application of OI_NPs significantly enhanced the phase shift ability of PFP and the optical characteristics of ICG, thus leading to a significant improvement in photoacoustic and ultrasonic imaging. When combined with near-infrared light and ultrasound, the application of OI_NPs led to improved anti-tumor effects on cancer cells, and significantly enhanced the expression of DAMPs, thus generating a long-term anti-tumor effect. CONCLUSION: The application of OI_NPs, loaded with appropriate cargo, may represent a novel strategy with which to increase anti-tumor effects, enhance immunological potency, and improve dual-mode imaging.