期刊
THERANOSTICS
卷 10, 期 7, 页码 2918-2929出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.41077
关键词
cisplatin; nanoparticle; HIF-1; acriflavine; combination therapy
资金
- Natural Science Foundation of China [81973257, 81801738, 81703446]
- Independent Innovation Foundation of Higher Education of China [2016JCTD109, 2016YXMS140, 2016YXMS147]
- National Postdoctoral Program for Innovative Talents [BX201600057]
- China Postdoctoral Science Foundation [2017M612474]
- Fundamental Research Funds for the Central Universities [HUST: 2018JYCXJJ008]
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-1 alpha/beta dimers 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.
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