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Dong-Yang Zhang

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Open access Jul 2026

A Multiple Enzyme‐Mimetic Platinum–Ruthenium Nanohybrid Prodrug Potentiates Chemo‐/Chemodynamic‐/Immuno‐Therapy of Hypoxic Tumors

Hypoxia in the tumor microenvironment (TME) is a hallmark of solid tumors and is tightly associated with the development of chemoresistance and immunosuppression, severely compromising the efficacy of mainstream clinical oncological treatments. Platinum‐based metallodrugs, especially oxaliplatin (Oxa), serve as first‐line chemotherapeutics in clinical practice. However, their clinical utility is greatly restricted by acquired drug resistance, insufficient tumor accumulation, and weak immunostimulatory capacity. Herein, we synthesize a platinum–ruthenium nanohybrid prodrug (denoted as PR) via self‐assembly, which integrates Oxa PR and ruthenium ions for synergistic chemo‐/chemodynamic‐/immunotherapy of hypoxic tumors. The PR nanohybrid possesses intrinsic multi‐enzyme activities (catalase, peroxidase, and glutathione peroxidase), enabling efficient oxygen generation, hydroxyl radical production, and glutathione depletion. These cascading events enhance chemosensitivity, trigger robust immunogenic cell death, and activate the cGAS‐STING signaling pathway. Furthermore, nanocatalytic modulation of the hypoxic TME alleviates hypoxia‐driven immunosuppression, downregulates PD‐L1 expression on cancer cells, and reinforces antitumor immune responses. In vitro and in vivo investigations demonstrate that PR nanohybrid exhibits superior anticancer efficacy over free Oxa and displays promising potential in combination with PD‐1 blockade therapy. These findings highlight the PR nanohybrid as a versatile TME‐modulating platform for hypoxic tumor treatment, offering a novel strategy to advance platinum‐based combination cancer therapy.

Huixi Yi, Yue Zheng, Nannan Fu et al. · Advanced Healthcare Material... · 0 citations

Jul 2026

Programmable 2D-to-3D structural transformation of DNA nanostructures triggered by single-stranded RNA.

Controllable structural transformation of DNA nanostructures offers substantial potential for molecular devices. Toehold-mediated strand displacement, a common strategy for driving such rearrangements, generally requires a dedicated toehold sequence to initiate the reaction, making the regulation of conformational changes in perfectly matched DNA systems challenging. To circumvent this limitation, we herein efficiently assembled a two-dimensional (2D) DNA triangle using only two short DNA strands. Inspired by the structural diversity of RNA, we found that strand displacement induced by the corresponding RNA sequence can alter the assembly pathway of the triangle without a toehold, leading to the formation of a three-dimensional (3D) RNA-DNA hybrid quadrilateral. All nanostructures and their transformation pathways were confirmed by cryogenic-electron microscopy (cryo-EM) and mass spectrometry (MS) analyses. Further, to investigate whether our designed transformable DNA nanostructure can serve as a target-specific signal reporting system, we developed a nucleic acid detection strategy based on isothermal amplification coupled with single-stranded RNA displacement-induced transformation of the DNA nanostructure (SDT), which successfully detected human papillomavirus (HPV) in clinical samples. Our experimental results demonstrate that RNA strand displacement provides new insights into constructing transformable DNA nanostructures and offers a novel design strategy for dynamic DNA nanostructures in molecular diagnostics.

Xiaoqiu Zheng, Tingyu Zhu, Bingbing Lyu et al. · Biosensors & bioelectronics · 0 citations