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    Nanoparticle formulations have proven effective for cisplatin delivery. However, the development of a versatile nanoplatform for cisplatin-based combination cancer therapies still remains a great challenge. Methods: In this study, we developed a one-pot synthesis method for a microporous organosilica shell-coated cisplatin nanoplatform using a reverse microemulsion method, and explored its application in co-delivering acriflavine (ACF) for inhibiting hypoxia-inducible factor-1 (HIF-1). Results: The resulting nanoparticles were tunable, and they could be optimized to a monodisperse population of particles in the desired size range (40-50 nm). In addition, organic mPEG2000-silane and tetrasulfide bond-bridged organosilica were integrated into the surface and silica matrix of nanoparticles for prolonged blood circulation and tumor-selective glutathione-responsive degradation, respectively. After reaching the tumor sites, cisplatin induced cancer cell death and activated HIF-1 pathways, resulting in acquired drug resistance and tumor metastasis. To address this issue, ACF was co-loaded with cisplatin to prevent the formation of HIF-1αdimers and suppress HIF-1 function. Hence, the efficacy of cisplatin was improved, and cancer metastasis was inhibited. Conclusion: Both in vitro and in vivo results suggested that this core-shell nanostructured cisplatin delivery system represented a highly efficacious and promising nanoplatform for the synergistic delivery of combination therapies involving cisplatin. © The author(s).

    Citation

    Xiaojuan Zhang, Chuanchuan He, Xiaoguang Liu, Yan Chen, Pengxuan Zhao, Chen Chen, Ruicong Yan, Minsi Li, Ting Fan, Bouhari Altine, Tan Yang, Yao Lu, Robert J Lee, Yongkang Gai, Guangya Xiang. One-pot synthesis of a microporous organosilica-coated cisplatin nanoplatform for HIF-1-targeted combination cancer therapy. Theranostics. 2020;10(7):2918-2929

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    PMID: 32194844

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