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[Display omitted] Ultrasound and X-rays possess remarkable tissue penetration capabilities, making them promising candidates for cancer therapy. Sonodynamic therapy, which utilizes ultrasound excitation, offers a safer alternative to radiotherapy and can be combined with X-rays to mitigate the adverse effects on normal tissues. In this study, we developed a bismuth-based heterostructure semiconductor (BFIP) to enhance the efficacy of radiotherapy and sonodynamic therapy in treating breast cancer. The semiconductor is fabricated through a two-step process involving the synthesis of porous spherical bismuth fluoride and partially reduced to bismuth oxyiodide. Then, followed by surface modification with amphiphilic polyethylene glycol, BFIP is fabricated. Incorporating heavy atoms in the BFIP enhances radiosensitivity. The BFIP exhibits superior carrier separation efficiency compared to bismuth fluoride, generating a substantial quantity of reactive oxygen species upon ultrasound stimulation. Moreover, the BFIP effectively depletes glutathione through coordination and hole-mediated oxidation pathways, disrupting the tumor microenvironment and inducing oxidative stress. Encouraging results are acquired in both in vitro cell and in vivo tumor models. Our study provides a de-risking strategy by utilizing ultrasound as a partial substitute for X-rays in treating deep-seated tumors, offering a viable research direction for constructing a unified nanoplatform. [ABSTRACT FROM AUTHOR]

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. Through the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF 3 within BZP, thereby facilitating the effective separation of electron–hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

A topological synthesis strategy is employed to develop an efficient bismuth-based semiconductor nano-photocatalyst (Bi 2 O 3 :S) for ferroptosis-mediated tumor phototherapy. [Display omitted] Ferroptosis-mediated tumor treatment is constrained by the absence of single-component, activatable multifunctional inducers. Given this, a topological synthesis strategy is employed to develop an efficient bismuth-based semiconductor nano-photocatalyst (Bi 2 O 3 :S) for tumor ferroptosis therapy. Photo-excited electrons can participate in the reduction reaction to produce harmful reactive oxygen species (ROS) when exposed to near-infrared light. Meanwhile, photo-excited holes can contribute to the oxidation reaction to utilize extra glutathione (GSH) in tumors. In the acidic tumor microenvironment, bismuth ions generated from Bi 2 O 3 :S may further cooperate with GSH to amplify oxidative stress damage and achieve biodegradation. Both promote ferroptosis by downregulating glutathione peroxidase 4 (GPX4) expression. Besides, sulfur doping optimizes its near-infrared light-induced photothermal conversion efficiency, benefiting its therapeutic effect. Thus, bismuth ions and holes synergistically drive photo-activable ferroptosis in this nanoplatform, opening up new avenues for tumor therapy. [ABSTRACT FROM AUTHOR]

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT. [ABSTRACT FROM AUTHOR]

Decreasing the scavenging capacity of reactive oxygen species (ROS) and enhancing ROS production are the two principal objectives in the development of novel sonosensitizers for sonodynamic therapy (SDT). Herein, we designed a protoporphyrin-sensitized bismuth-based semiconductor (P-NBOF) as a sonosensitizer to generate ROS and synergistically depleted glutathione for enhanced SDT against tumors. The bismuth-based nanomaterial (NBOF) is a wide-bandgap semiconductor. Sensitization by protoporphyrin made it easier to excite electrons under ultrasonic stimulation, and the energy of the lowest unoccupied electron orbital in protoporphyrin was higher than the conduction-band energy of NBOF. Under ultrasound excitation, the excited electrons in the protoporphyrin were injected into the conduction band of the NBOF, increasing its reducing ability leading to the production of more superoxide anion radicals and also helping to increase the charge separation of protoporphyrin leading to the production of more singlet oxygen. Meanwhile, P-NBOF continuously depleted glutathione, which was not only conducive to breaking the redox balance of the tumor microenvironment to enhance the therapeutic efficacy of SDT, but also promoted its degradation and metabolism. The construction of this P-NBOF sonosensitizer thus provided an effective strategy to enhance SDT for tumors. To enhance the efficacy of sonodynamic tumor therapy, we developed a degradable protoporphyrin-sensitized bismuth-based nano-semiconductor (P-NBOF) by optimizing the band structure and glutathione-depletion ability. Protoporphyrin in P-NBOF under excitation preferentially generates free electrons, which are then injected into the conduction band of NBOF, improving the reducing ability of NBOF and promoting the separation of electron-hole pairs, thereby enhancing the production capacity of reactive oxygen species. Furthermore, P-NBOF can deplete glutathione, reduce the scavenging of reactive oxygen species, and reactivate and amplify the effect of sonodynamic therapy. The construction of the nanotherapeutic platform provides an option for enhancing sonodynamic therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A fresh type of metal-sensitized sonocatalyst was designed. • The light/sono-responsive nanoplatform can generate adequate ROS and heat. • Generated ROS and heat mutualistically trigger immunogenic cell death. • The sonocatalyst activates immune response, hindering tumor growth and metastasis. Sonodynamic tumor therapy is limited by inefficient sonosensitizers and complex tumor microenvironments. Given this, a concept of metal-sensitized sonocatalyst is proposed and defined as a catalyst based on the metal sensitization effect of noble metals to advance semiconductor sonocatalytic activity. We load Au nanorods onto wide-bandgap semiconductor bismuth oxide to favor its sonocatalytic properties for supporting the concept's practicality. In the catalytic nano-system, Au nanorods improve the ability of bismuth oxide to separate electrons and holes under ultrasound, promoting multifarious reactive oxygen species (ROS) generation and enhancing the photothermal effect. Synergistically, bismuth oxide can consume intratumoral overexpressed glutathione, further disrupting the redox balance. Thus, ROS and heat can directly induce immunogenic cell death, reversing tumor immunosuppressive microenvironment in concert and promoting dendritic cell maturation and CD8+ T cell infiltration. The proposed metal-sensitized sonocatalyst will open up new avenues for sonocatalytic therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ce and S-doped Bi 2 O 3 nanosheets (BOSC) with oxygen defects are designed and synthesized. • Oxygen vacancies enhance the charge transfer and light absorption capacity. • Cascade conversion of reactive oxygen species is realized via band bending. • BOSC exhibits a variety of enzyme-like activities, leading to tumor oxidative stress amplification. • BOSC can initiate inflammatory programmed cell death, known as PANoptosis. Photocatalytic therapy (PCT) is a minimally invasive technique that utilizes reactive oxygen species (ROS) to selectively and optically impair tumor cells. However, the limited efficacy of photocatalysts hinders their more comprehensive application. In this study, we successfully synthesized Ce and S-doped Bi 2 O 3 (BOSC) nanosheets through topological synthesis. BOSC exhibits CAT-like and POD-like enzyme activities and can generate ROS and heat upon near-infrared light irradiation, thereby amplifying tumor oxidative stress. Introducing rare earth Ce element enhances light absorption, introduces oxygen vacancies, reduces bandgap, and facilitates charge separation. This Ce-doping also modifies the band position and Fermi level of BOSC, resulting in increased band bending at the solid–liquid interface, enabling a cascade reaction of ROS and enhancing ROS production. Additionally, BOSC demonstrates multiple enzyme activities by depleting GSH and catalyzing the production of ROS and O 2 from endogenous H 2 O 2 , thereby exacerbating cellular oxidative damage. The synergistic effect of BOSC post-illumination induces panoptosis, thereby improving the therapeutic efficacy against tumors. This strategy, involving the modulation of band structure and band bending through ion doping to introduce oxygen defects into the photosensitizer, provides a viable approach to enhance tumor phototherapy. [ABSTRACT FROM AUTHOR]