Recently, the team of Associate Professor Jing Quan from the College of Biological and Medical Engineering, in collaboration with the team of Director Peng Sun from Shanghai Tongren Hospital affiliated to Shanghai Jiao Tong University School of Medicine, published a research paper titled “CaO₂-based AuPt Bimetallic Nanozymes with Cascade CatalysisforSynergistic Chemodynamic/Photothermal/Immunotherapy” in Chemical Engineering Journal. This work provides a novel strategy for tumor therapy.
Nanozyme-based chemodynamic therapy (CDT) has become a research hotspot in oncotherapy in recent years due to its high safety, independence from external oxygen supply, and ability to modulate the tumor microenvironment. CDT relies on Fenton or Fenton-like reactions to convert endogenous H₂O₂ into highly toxic reactive oxygen species (ROS) that kill tumor cells. However, clinical translation faces two major bottlenecks: (1) insufficient catalytic activity of nanozymes, and (2) extremely low H₂O₂ concentration in the tumor microenvironment (only 50–100 × 10⁻⁶ M), which is inadequate to generate sufficient ROS. Moreover, a single treatment modality cannot completely eliminate tumors or prevent recurrence and metastasis, severely limiting clinical application. Therefore, constructing efficient self supplying H₂O₂ nanozyme systems integrating multimodal synergistic therapy has become a key research direction in cancer nanomedicine. To address these challenges, the research team leveraged interdisciplinary collaboration between medicine and engineering and developed a CaO₂ based AuPt bimetallic self cascade nanozyme system, named CaO₂/AuPt@BSA (CAPB), which achieves triple synergistic antitumor therapy combining chemodynamic, photothermal, and immunotherapy. The corresponding authors are Jing Quan and Peng Sun; the co first authors are graduate students Wentao Liu and Lili Zhu from the College of Biological and Medical Engineering.
(Scheme 1 (a) Schematic illustration of the preparation of CAPB nanozymes; (b) Mechanism of antitumor action.)
The CAPB nanozyme system was designed based on the acidic and metabolic characteristics of the tumor microenvironment. Using a calcium chloride method, CaO₂ nanosphere cores with good biocompatibility were constructed, integrated with Au and Pt bimetallic nanozymes, and surface encapsulated with BSA. This endows the system with excellent tumor targeting and physical stability (average particle size ~200 nm, stable over 7 days). The system precisely attacks tumors through an efficient self cascade catalytic reaction: upon entering the acidic tumor microenvironment, the Au nanozyme consumes glucose to achieve “starvation therapy” and generates H₂O₂; then the Pt nanozyme catalytically converts H₂O₂ into highly toxic hydroxyl radicals (•OH) to enhance chemodynamic therapy (CDT). At the same time, Ca²⁺ released from CaO₂ decomposition induces severe mitochondrial dysfunction.
In terms of energy conversion and catalytic performance, the Au nanozyme also endows the system with excellent photothermal conversion efficiency (36.3%). Under 808 nm laser irradiation, a 400 μg/mL CAPB solution exhibits a temperature increase of approximately 38 °C, enabling not only photothermal ablation (PTT) of tumors but also significant acceleration of cascade catalytic kinetics (K<sub>m</sub> = 39.178 ± 7.656 mM, V<sub>max</sub> = 2.249×10⁻⁶ ± 1.923×10⁻⁷ M min⁻¹). In vitro experiments confirmed that the system can precisely identify and kill 4T1 tumor cells, achieving an apoptosis rate of 58.8% under photothermal enhancement, while exhibiting low toxicity to normal cells.
Regarding in vivo antitumor efficacy and immune activation, the CAPB nanozyme demonstrates robust synergistic therapeutic capability. Animal experiments showed that the nanozyme accumulated at the tumor site 8 hours after administration. Combined with αPD L1 antibody therapy, it achieved a primary tumor inhibition rate of 82.7%, which is 1.67 fold higher than that of immunotherapy alone, and a distant tumor inhibition rate of 79.18%. This remarkable efficacy is attributed to immunogenic cell death (ICD) induced synergistically by CDT and PTT, which effectively promotes the release of damage associated molecular patterns (DAMPs). The proportions of mature dendritic cells (DCs) and CD8⁺ T cells in vivo increased to 2.60 fold and 1.73 fold those of the control group, respectively, and key immune factors such as TNF α and IL 12 were upregulated. This triple synergistic strategy combining catalytic, photothermal, and immunotherapeutic actions significantly inhibits tumor growth and metastasis while exhibiting favorable biosafety, providing a strong scientific basis and promising application prospects for multimodal synergistic tumor therapy.
This study was supported by several research grants, including the “Shanghai Tongren Hospital – Donghua University Medical Engineering Interdisciplinary Project”. It exemplifies the important practice and value of deep collaboration between a university and a hospital in advancing medical innovation and supporting high quality regional development.
Original link: https://doi.org/10.1016/j.cej.2026.17256
