Palladium-Catalyzed Hydrogenation of Black Barium Titanate for Multienzyme-Piezoelectric Synergetic Tumor Therapy.

Piezocatalytic tumor therapy is an emerging reactive oxygen species (ROS)-generating therapeutic approach that relies on piezoelectric polarization under ultrasound (US) irradiation. Optimizing ROS production is a primary objective for enhancing treatment efficiency. In this study, oxygen-vacancy-rich Pd-integrated black barium titanate (BTO) nanoparticles are rationally engineered to boost the ROS generation efficiency via the introduction of Pd. Pd-catalyzed hydrogenation at low temperatures narrows the bandgap of BTO and reduces the recombination rate of electron-hole pairs. Furthermore, Pd has dual-enzyme-mimicking characteristics, including peroxidase- and catalase-mimicking activities, which further heighten the therapeutic efficacy by enhancing ROS production and reversing the hypoxic tumor microenvironment. Importantly, the dual enzymatic activity of Pd can be amplified by multiple redox processes sparked by the piezoelectric potential under US stimulation, resulting in bilaterally enhanced multienzyme-piezoelectric synergetic therapy. In vitro and in vivo results confirm high tumor inhibition in murine breast cancer cells. This work stresses the critical effects of defect engineering-optimized piezodynamic tumor therapy.

Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis.

BACKGROUND: Magnetic hyperthermia (MHT)-mediated thermal ablation therapy has promising clinical applications in destroying primary tumours. However, traditional MHT still presents the challenges of damage to normal tissues adjacent to the treatment site and the destruction of tumour-associated antigens due to its high onset temperature (> 50 °C). In addition, local thermal ablation of tumours often exhibits limited therapeutic inhibition of tumour metastasis. RESULTS: To address the above defects, a hybrid nanosystem (SPIOs + RPPs) was constructed in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate supermagnetic iron oxide nanoparticle (SPIO)-mediated mild MHT (< 44 °C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell. Because of the cavitation effect of microbubbles produced by RPPs, the temperature threshold of MHT could be lowered from 50℃ to approximately 44℃ with a comparable effect, enhancing the release and exposure of damage-associated molecular patterns (DAMPs). The exposure of calreticulin (CRT) on the cell membrane increased by 72.39%, and the released high-mobility group B1 (HMGB1) increased by 45.84% in vivo. Moreover, the maturation rate of dendritic cells (DCs) increased from 4.17 to 61.33%, and the infiltration of cytotoxic T lymphocytes (CTLs) increased from 10.44 to 35.68%. Under the dual action of mild MHT and immune stimulation, contralateral and lung metastasis could be significantly inhibited after treatment with the hybrid nanosystem. CONCLUSION: Our work provides a novel strategy for enhanced mild magnetic hyperthermia immunotherapy and ultrasound imaging with great clinical translation potential.