Conventional sonodynamic therapy is unavoidably limited by the tumor microenvironment, although many sonosensitizers have been developed to improve them to a certain extent. Given this, a concept of sonocatalytic hydrogen evolution is proposed, which is defined as an oxygen‐independent therapeutics. To demonstrate the feasibility of the concept, the narrow‐bandgap semiconductor bismuth sulfide (Bi2S3) is selected as the sonocatalyst and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, the Pt nanoparticles help to capture sonoexcited electrons, whereas intratumoral overexpressed glutathione (GSH), as a natural hole sacrificial agent, can consume sonoexcited holes, which greatly improves the charge‐separation efficiency and promotes controllable and sustainable H2 generation. Even under hypoxic conditions, the Pt‐Bi2S3 nanoparticles can also produce sufficient H2 under ultrasound irradiation. Mechanistically, mitochondrial dysfunction caused by H2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, the Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O2 to relieve tumor hypoxia, thus being synergistic with GSH depletion to reverse tumor immunosuppressive microenvironment. The proposed sonocatalysis‐mediated therapy will provide a new direction to realize facile and efficient cancer therapy.

Rational Design of Platinum–Bismuth Sulfide Schottky Heterostructure for Sonocatalysis‐Mediated Hydrogen Therapy

The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO3 /Bi2 WO6 (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h+ )-electron (e- ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h+ can trigger the decomposition of H2 O2 to generate O2 for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O2 self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence. 

Reshaping the Tumor Immune Microenvironment Based on a Light‐Activated Nanoplatform for Efficient Cancer Therapy

The immune checkpoint blockade (ICB) therapy has revolutionized the field of cancer treatment, while low response rates and systemic toxicity limit its clinical outcomes. With the rapid advances in nanotechnology and materials science, various types of biomaterials have been developed to maximize therapeutic efficacy while minimizing side effects by increasing tumor antigenicity, reversing immunosuppressive microenvironment, amplifying antitumor immune response, and reducing extratumoral distribution of checkpoint inhibitors as well as enhancing their retention within target sites. In this review, we reviewed current design strategies for different types of biomaterials to augment ICB therapy effectively and then discussed present representative biomaterial-assisted immune modulation and targeted delivery of checkpoint inhibitors to boost ICB therapy. Current challenges and future development prospects for expanding the ICB with biomaterials were also summarized. We anticipate this review will be helpful for developing emerging biomaterials for ICB therapy and promoting the clinical application of ICB therapy.

Boosting Checkpoint Immunotherapy with Biomaterials.

Dual targeting procyanidin nanoparticles with glutathione response for colitis treatment

Oxygen-boosted biomimetic nanoplatform for synergetic phototherapy/ferroptosis activation and reversal of immune-suppressed tumor microenvironment.

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand-new artificial metalloprotein nanoanalogues is developed via reasonable integration of a "phototherapy-enzymatic" RuO2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO2 -hybridized OVA nanoanalogues (RuO2 @OVA NAs). The RuO2 @OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near-infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO2 @OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O2 ). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T-lymphocyte-associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth.

The invention discloses a preparation method and application of a ruthenium dioxide composite ovalbumin nano material; the nano material is prepared by firstly synthesizing nano ruthenium dioxide by taking ruthenium trichloride hydrate and ammonia water as raw materials and then compounding nano ruthenium dioxide on ovalbumin. The preparation method is simple and convenient to operate, raw materials are cheap and easy to obtain, and the prepared nano material has the advantages of small cytotoxicity, good biocompatibility and the like. In addition, the ruthenium dioxide nano material has an absorption function in a near infrared region, and the nano material compounded on ovalbumin has good water solubility, good anti-tumor immunity induction and photosensitive effect, active oxygen can begenerated under the irradiation of infrared or near infrared light; hydrogen peroxide in a tumor can be catalyzed to generate oxygen, thereby solving the problem of tumor hypoxia and being beneficialto further photodynamic treatment. The ruthenium dioxide composite ovalbumin nano material can be used for photothermal photodynamic immunity combined treatment of cancer and has wide application prospect in the technical field of cancer treatment.

Preparation method and application of ruthenium dioxide composite ovalbumin nano material

The invention discloses an aggregation-induced emission carbon quantum dot and a preparation method thereof. The method includes the following steps that hemoglobin and sulfuric acid is mixed to prepare turbid liquid, the turbid liquid reacts under heating and stirring conditions, and mixed liquid of reaction products is obtained. An inorganic alkali aqueous solution is added into the mixed liquidof the products, and the mixed liquid is cooled to 0 DEG C, wherein the pH of the mixed liquid is 7; the cooled mixed liquid is filtered, obtained mother liquor is concentrated, ethyl alcohol is added into the mother liquor to remove sulfate, remaining mother liquor is concentrated and freeze-dried, and the aggregation-induced emission carbon quantum dot is obtained, wherein the particle size ofthe prepared aggregation-induced emission carbon quantum dot is 4-8 nm. The process is simple, the reaction condition is mild, the energy consumption is low, the fluorescence performance is good, andquenching is difficult. Aggregation-induced emission of the carbon quantum dot is achieved, and application and popularization of the quantum dot are facilitated.

Aggregation-induced emission carbon quantum dot and preparation method thereof

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Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth.

Preparation method and application of ruthenium dioxide composite ovalbumin nano material

Aggregation-induced emission carbon quantum dot and preparation method thereof