Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphine-conjugated catalase (CAT-TCPP). The formed CAT-TCPP/FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O2 generation from tumor endogenous H2O2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.
The treatment of multidrug-resistant (MDR) infections remains a major challenge faced by humans. Effective phototherapy, such as photothermal and photodynamic therapies, can inhibit drug-resistant bacteria and is considered an innovative treatment approach that can replace antibiotics. In this study, molybdenum disulfide (MoS2) nanoflowers, photosensitizer chlorin-e6 (Ce6), autogenic oxygen nanocalcium oxide (CaO2), and MOF material (ZIF-8) were used to construct MoS2–Ce6–CaO2@ZIF-8 (MCC@ZIF-8), an autogenic oxygen multifunctional nanosystem. This system exhibited photothermal and photodynamic antibacterial activities in the active near-infrared (808 nm) and visible (660 nm) regions of the spectrum. The experimental results indicated that the nanosystem was hexahedral, its zeta potential was +38 ± 1.1 mV, particle size was approximately 310 nm, and photothermal conversion efficiency was 47%. In the experiment, this nanosystem showed >95% antibacterial effect against MDR Escherichia coli and Staphylococcus aureus. Furthermore, it could inhibit the expression of bacterial base excision repair, tyrosine metabolism, glutathione metabolism, and other genes. The hydrogel system MCC@ZIF-8@BBR/CS/β-GP (MCC@ZIF-8@BCβ) further promoted wound healing in the infected mice. These findings confirm the significant antibacterial effect of the autogenic oxygen multifunctional nanocomposite and lay the foundation for the practical application of this nanosystem in clinical practice.