Ultrasmall gold-encapsulated mesoporous platinum to promote photodynamic/catalytic therapy through cascade enzyme-like reactions.

Mesoporous platinum (mPt) nanozyme possessed enzyme-like property of catalase (CAT) and peroxidase (POD), but the insufficient hydrogen peroxide (H2O2) concentration severely restricted its application in photodynamic therapy (PDT) and catalytic therapy. Herein, by depositing ultrasmall gold nanoparticles (AuNPs) and modifying photosensitizer IR808, a multifunctional nanozyme (mPt@Au-IR808) was designed to promote PDT/catalytic therapy through cascade enzyme-like reactions of glucose oxidase (GOx) and CAT/POD. In tumor microenvironment, the CAT-like oxygen (O2) generation improved the PDT efficacy, and the POD-like hydroxyl radical (·OH) generation achieved endogenous catalytic therapy. Using the GOx/CAT-like activities and endogenous H2O2, the yields of singlet oxygen and ·OH were significantly promoted. Furthermore, mPt@Au-IR808 showed higher photothermal conversion efficiency (41.2%) than mPt (36.1%). By combining the photothermal therapy and enhanced PDT/catalytic therapy, the developed mPt@Au-IR808 nanozyme showed excellent anti-tumor efficacy, which will be promising as cascade nanozyme to promote photo/catalytic therapy.

Wang T ，Liu T ，Li Z ，Wu D ，Zhao X ，Zeng L ... -  《-》

Dual-activity nanozyme as an oxygen pump to alleviate tumor hypoxia and enhance photodynamic/ NIR-II photothermal therapy for sniping oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region, and its treatment is limited by hypoxia and inadequate oxygen supply. Continuous oxygen delivery combined with photodynamic therapy (PDT) is the key to addressing this issue. Here, a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform was designed to serve as an "oxygen pump" to alleviate tumor hypoxia for synergistic photodynamic/photothermal therapy (PTT). In this design, the photosensitizer chlorin e6 (Ce6) is covalently linked to the Au@Pt nanozyme for PDT treatment. The Au@Pt nanozyme exhibits catalase-like activity, continuously decomposing H2O2 in the tumor microenvironment to enhance O2 levels, thereby achieving efficient PDT. Furthermore, Au@Pt can perform PTT and increase oxygen levels under NIR-II light to further promote PDT. The Au@Pt nanozyme also exhibits peroxidase-like activity, generating ·OH for chemodynamic therapy (CDT). Additionally, HN-1 guides the direction of "sniping" OSCC, and its high specificity benefits Au@Pt-Ce6-HN-1 at the tumor site. Au@Pt-Ce6-HN-1 exhibits bright fluorescence (FL), strong CT signal, and photothermal imaging capabilities, laying the foundation for subsequent guided PDT/PTT. This nanoplatform, which combines advantages such as continuous oxygen production, tumor targeting, and multimodal imaging, is expected to provide valuable insights into the treatment of OSCC. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of OSCC are challenging. We report a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform, serving as an "oxygen pump" to guide photodynamic therapy (PDT) and photothermal therapy (PTT) for OSCC. This nanoplatform targets OSCC for preoperative CT diagnosis and offers fluorescence visualization for surgical navigation, demonstrating potential in clinical cancer detection and surgery guidance. This innovative approach addresses OSCC hypoxia and enhances treatment efficacy through continuous oxygen production, tumor targeting, and multimodal imaging, significantly improving patient outcomes in OSCC treatment.

Li X ，Hao M ，Liu A ，Li L ，Nešić MD ，Yang B ，Liu W ，Lin Q ... -  《-》

One-pot synthesis and covalent conjugation of methylene blue in mesoporous silica nanoparticles - A platform for enhanced photodynamic therapy.

Kirla H ，Wu J ，Hamzah J ，Henry DJ ... -  《-》

Ultrasmall Au/Pt-loaded biocompatible albumin nanospheres to enhance photodynamic/catalytic therapy via triple amplification of glucose-oxidase/catalase/peroxidase.

Hao R ，Zhang G ，Zhang J ，Zeng L ... -  《-》

A multifunctional cascade gas-nanoreactor with MnO(2) as a gatekeeper to enhance starvation therapy and provoke antitumor immune response.

Glucose oxidase (GOx)-mediated starvation therapy is an effective tumor treatment that blocks energy and activates the immune response. However, the insufficient tumor immunogenicity and immunosuppressive tumor microenvironment (TME) limited its therapeutic efficacy. To address this, we have designed a multifunctional cascade gas-nanoreactor with a MnO2 coating, which serves as an out gatekeeper to encapsulate both GOx and a carbon monoxide (CO) donor (denoted as GCM). Due to the protective effect of MnO2 coating, GCM maintains better stability in normal physiological environments, enhancing the catalytic activity of GOx and minimizing toxic side effects. Upon accumulation in the tumor, the degradation of MnO2 coating exposes the GOx enzyme, thereby initiating a cascade catalysis reaction to generate hydrogen peroxide (H2O2) and release CO in the hypoxic conditions. Additionally, the released Mn2+ reacts with H2O2 to generate toxic hydroxyl radical (•OH) as chemodynamic therapy (CDT). The synergistic treatments of starvation therapy, CO gas therapy and CDT effectively kill cancer cells and amplify immunogenic cell death (ICD), maturing DC cells and activating anti-tumor immune response. Furthermore, the released CO increases M1 macrophages infiltration and reduces myeloid-derived suppressor cells (MDSCs) infiltration, thus reversing the immunosuppressive TME. This multifunctional gas-nanoreactor provides a strategy for CO gas generation to trigger a robust anti-tumor immune response and has the potential for clinical application in cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A multifunctional cascade gas-nanoreactor with a MnO2 gatekeeper was developed to perform synergistic treatments involving starvation therapy, CO gas therapy and chemodynamic therapy (CDT) for tumor elimination. The MnO2 gatekeeper enhanced the catalytic activity of GOx within the nanoreactor by generating oxygen, thereby minimizing toxic side effects after intravenous injection. The gas-nanoreactor amplified ICD through synergistic treatments to mature DC cells and activate anti-tumor immune response. Furthermore, the released CO could reverse the immunosuppression of the TME to enhance cancer immunotherapy. The combination strategy utilizing the gas-nanoreactor demonstrates clinical potential for facilitating cancer immunotherapy.

Ren H ，Bai Y ，Liu Z ，Ma C ，Tao X ，Wang Q ，Lian H ，Li X ... -  《-》