One-pot synthesis of a microporous organosilica-coated cisplatin nanoplatform for HIF-1-targeted combination cancer therapy

• Published in: Theranostics 2020-01, Vol.10 (7), p.2918-2929
• Main Authors: Zhang, Xiaojuan, He, Chuanchuan, Liu, Xiaoguang, Chen, Yan, Zhao, Pengxuan, Chen, Chen, Yan, Ruicong, Li, Minsi, Fan, Ting, Altine, Bouhari, Yang, Tan, Lu, Yao, Lee, Robert J, Gai, Yongkang, Xiang, Guangya
• Format: Article
• Language: English
• Subjects: A549 Cells; Acriflavine - pharmacology; Animals; Antineoplastic Agents - pharmacology; Cancer therapies; Chemotherapy; Cisplatin - pharmacology; Drug Carriers - chemical synthesis; Drug Therapy, Combination; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Metastasis; Mice; Microemulsions; Nanoparticles - chemistry; Neoplasms - drug therapy; Photodynamic therapy; Research Paper; Silicon Dioxide - chemistry; Surfactants; Vascular endothelial growth factor
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.41077

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. : 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). : 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-1α/β dimers and suppress HIF-1 function. Hence, the efficacy of cisplatin was improved, and cancer metastasis was inhibited. : Both and 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.