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Under appropriate parameters, medical ultrasound can induce immunogenic cell death via thermal and/or nonthermal effects, activating a certain degree of antitumor immunity in cancer mouse models. Different types of sono-responsive biomaterials have been coupled to immunomodulators, which can be released into the tumor microenvironment under ultrasonic irradiation. Systems that integrate sonosensitizers and immunologically active agents generating reactive oxygen species can result in a combined therapeutic effect upon ultrasound exposure in certain cancer mouse models. Following ultrasound treatment, certain engineered bacterial or cellular approaches can trigger antitumor immune responses in certain cancer mouse models. Current cancer immunotherapy suffers from limited response rates, variable efficacies, and immune-related adverse events. One alternative strategy is to use emerging sono-immunotherapeutic approaches via biomedical ultrasound, which can serve as a switch to induce direct therapy as well as further antitumor immune responses. Understanding the process of sono-immunomodulation and the potencies of several novel strategies based on sono-immunomodulatory agents can accelerate the development and transformation of immunotherapy for certain cancers and, ideally, for other diseases. Owing to its remarkable ease of use, ultrasound has recently been explored for stimulating or amplifying immune responses during cancer therapy, termed 'sono-immunotherapy'. Ultrasound can cause immunogenic cell death in cancer cells via thermal and nonthermal effects to regulate the tumor microenvironment, thereby priming anticancer immunity; by integrating well-designed biomaterials, novel sono-immunotherapy approaches with augmented efficacy can also be developed. Here, we review the advances in sono-immunotherapy for cancer treatment and summarize existing limitations along with potential trends. We offer emerging insights into this realm, which might prompt breakthroughs and expand its potential applications to other diseases. [ABSTRACT FROM AUTHOR]

Cancer is a serious health problem to be solved. With the development of biomaterials, enhanced diagnostic and controllable therapeutic strategies for cancer have emerged, revealing encouraging results with a promising future. Due to its outstanding tissue penetration and controllability, along with a series of bioeffects on tissues, ultrasound (US), as a common medical technology, has been regarded as an effective tool against cancer, and its use has promoted the exploration of US‐sensitive biomaterials. In this review, the bioeffects of US are first introduced and then the main US‐sensitive biomaterials (containing cavitation nuclei, sonosensitizers, and US‐responsive macromolecular systems) used to treat cancer, followed by a summary of several applications based on US‐sensitive biomaterials, from diagnosis to therapy. Finally, the emerging challenges in this field that need to be overcome are highlighted. This review reports the progress of US‐sensitive biomaterials, providing new possibilities in cancer theranostics and thus benefiting patients. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy effect can be greatly enhanced by other methods to induce immunogenic cell death (ICD), which has profoundly affected immunotherapy as a highly efficient paradigm. However, these treatments have significant limitations, either by causing damage of the immune system or limited to superficial tumors. Sonodynamic therapy (SDT) can induce ICD to promote immunotherapy without affecting the immune system because of its excellent spatiotemporal selectivity and low side effects. Nevertheless, SDT is still limited by low reactive oxygen species yield and the complex tumor microenvironment. Recently, some emerging SDT‐based nanomedicines have made numerous attractive and encouraging achievements in the field of cancer immunotherapy due to high immunotherapeutic efficiency. However, this cross‐cutting field of research is still far from being widely explored due to huge professional barriers. Herein, the characteristics of the tumor immune microenvironment and the mechanisms of ICD are firstly systematically summarized. Subsequently, the therapeutic mechanism of SDT is fully summarized, and the advantages and limitations of SDT are discussed. The representative advances of SDT‐based nanomedicines for cancer immunotherapy are further highlighted. Finally, the application prospects and challenges of SDT‐based immunotherapy in future clinical translation are discussed. [ABSTRACT FROM AUTHOR]

Gas‐mediated sonodynamic therapy (SDT) has the potential to become an effective strategy to improve the therapeutic outcome and survival rate of cancer patients. Herein, titanium sulfide nanosheets (TiSX NSs) are prepared as cascade bioreactors for sequential gas–sonodynamic cancer therapy. TiSX NSs themselves as hydrogen sulfide (H2S) donors can burst release H2S gas. Following H2S generation, TiSX NSs are gradually degraded to become S‐defective and partly oxidized into TiOX on their surface, which endows TiSX NSs with high sonodynamic properties under ultrasound (US) irradiation. In vitro and in vivo experiments show the excellent therapeutic effects of TiSX NSs. In detail, large amounts of H2S gas and reactive oxygen species (ROS) can simultaneously inhibit mitochondrial respiration and ATP synthesis, leading to cancer cell apoptosis. Of note, H2S gas also plays important roles in modulating and activating the immune system to effectively inhibit pulmonary metastasis. Finally, the metabolizable TiSX NSs are excreted out of the body without inducing any significant long‐term toxicity. Collectively, this work establishes a cascade bioreactor of TiSX NSs with satisfactory H2S release ability and excellent ROS generation properties under US irradiation for programmed gas–sonodynamic cancer therapy. [ABSTRACT FROM AUTHOR]

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)‐mediated cancer therapy. Herein, vanadium‐based nanocatalysts, hydrogen vanadium bronzes (HXV2O5, for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi‐functional catalytic activity in decomposing H2O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS‐mediated cancer therapies. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT)-induced immunogenic cell death (ICD) features the potential for cancer therapy. However, SDT alone is weak to trigger robust ICD. Herein, PEGylation manganese-doping titanium disulfide nanosheets (PEG-Mn: TiSx NSs, abbreviated as MnTiS-PEG) are fabricated as a kind of cascade bioreactor for sequential gas therapy (GT)-enhanced SDT. MnTiS-PEG could release H 2 S gas to first induce cell apoptosis via mitochondria damage, accompanied by an oxidative degradation that would boost the efficacy of the sonodynamic effects under US irradiation, which is much superior to the commercial TiO 2. With Mn2+ releasing, such cascade process could further trigger satisfactory ICD and enhance dendric cells (DCs) maturation. In vitro and in vivo results illustrate the outstanding outcomes of such sequential GT-SDT along with a series of immune responses. Considering the possible immune tolerance, anti-programmed cell death-1 (αPD-L1), an immune checkpoint inhibitor, is employed subsequently to further inhibit tumor growth. It is found that this combination displays not only an excellent therapeutical performance on the primary tumors, but also an abscopal effect at the same time. Briefly, our work establishes a cascade bioreactor for the programmed GT-SDT with satisfactory immune responses, which provides an effective method for enhancing SDT and immunotherapy. [Display omitted] • Manganese-doping titanium disulfide (MnTiS) are fabricated as a cascade bioreactor for gas-sonodynamic therapy (GT-SDT). • MnTiS-PEG could release H 2 S to induce cell apoptosis, accompanied by an oxidative degradation that would boost SDT efficacy. • With Mn2+ release, such cascade process could trigger satisfactory ICD and enhance dendric cell (DC) maturation. • In vitro and in vivo results illustrate the outstanding outcomes of such sequential GT-SDT with a series of immune responses. • The combination therapy with αPD-L1 displays an excellent therapeutical outcome for both the primary and the distant tumors. [ABSTRACT FROM AUTHOR]

• Mechanism and prominent advantages of SDT for cancer treatment are systematically dissected. • Immense potential of MOFs-based SDT is specifically highlighted. • The latest innovative progresses about MOFs-based SDT are comprehensively summarized. • Challenge and perspective of MOFs-based SDT in clinical translation are deeply discussed. Sonodynamic therapy (SDT) is a promising cancer therapy due to its noninvasiveness, negligible side effects, and deep tissue penetration. However, the effect of SDT is significantly compromised by the tumor hypoxic microenvironment and the low bioavailability of sonosensitizers, and the tumor inhibition efficiency is far from the expected effect in vivo. Metal organic frameworks (MOFs) have attracted considerable attention in the biomedical and energy fields in recent years thanks to their many interesting tunable physicochemical properties. Especially, MOFs can be used as a powerful and versatile toolbox to address the bottlenecks faced by SDT. In the past few years, MOFs-based SDT have achieved many encouraging results because of the great potential of MOFs, and the number of associated research works has grown exponentially in this emerging field. Therefore, we strive to provide a timely review thoroughly summarizing the progress of MOFs-based SDT, and to improve further development of this exciting SDT field. In this paper, we comprehensively review, and analysis various solutions adopted by MOFs to overcome the problems of SDT, including MOFs as super-efficient sonosensitizer carriers, metal ion-optimized MOFs to enhance SDT, MOFs as multifunctional platforms for synergistic therapy, and MOFs as templates to prepare efficient nano-sonosensitizers. Finally, we discuss the prospects and difficulties for clinical translation of MOFs-based SDT. [ABSTRACT FROM AUTHOR]