Superstable and Large-Scalable Organosilica-Micellar Hybrid Nanosystem via a Confined Gelation Strategy for Ultrahigh-Dosage Chemotherapy
Superstable and Large-Scalable Organosilica-Micellar Hybrid Nanosystem via a Confined Gelation Strategy for Ultrahigh-Dosage Chemotherapy
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DOI：
10.1021/acs.nanolett.1c02342
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发表时间：
2021-11-24
期刊：
影响因子：
10.8
通讯作者：
Shi, Jianlin
中科院分区：
文献类型：
--
作者：
Niu, Dechao;He, Jianping;Shi, Jianlin
虽然各种药物纳米载体已经被开发出来用于治疗实体瘤，但其临床转化受到大量生产的困难和体内毒性效应的不可预测的限制。本文发展了一种简单的“限制凝胶”策略，用于批量生产临界胶束浓度(CMC)不可检测的智能Pluronic有机硅胶束(简称IPOM)，其特征是嵌段共聚物自组装导致核限制，硅烷与低聚物骨架的内部水解-缩合，以及二硫骨架与核凝胶的氧化交联。具有精确谷胱甘肽(GSH)响应性的多西紫杉醇IPOms(DTX@IPOms)不仅在健康昆明小鼠模型中表现出超高的耐受量(360 mg/kg)，而且在超大剂量(50 mg/kg)的皮下和原位肿瘤模型中都显示出显著的抑瘤效果。目前的受限凝胶策略为在未来的临床转化中设计和批量生产低毒和高效的有机-无机杂化纳米微球提供了一条新的途径。
Although various drug nanocarriers have been developed for treating solid tumors, their clinical transformation is greatly limited by the difficulties in quantity production and unpredictable in vivo toxic effects. Herein, a facile "confined-gelation" strategy is developed to quantity-produce intelligent pluronic organosilica micelles (designated as IPOMs) with an undetectable critical micelle concentration (CMC), which features the self-assembly induced core confinement by block copolymers, the inner hydrolysis-condensation of silane to the oligomer skeleton, and oxidative cross-linking of disulfide skeleton to core gelation. The docetaxel-loaded IPOMs (DTX@IPOMs) with precise glutathione (GSH) responsiveness not only display an ultrahigh tolerated dose (360 mg/kg) in healthy Kunming mice model but also exhibit a remarkable tumor inhibition efficacy in both subcutaneous and orthotopic mice tumor models upon an extraordinarily large dosage (50 mg/kg). The present confined-gelation strategy provides a novel pathway to design and quantity-produce low-toxic and high-efficacy organic-inorganic hybrid nanodrugs in future clinical transformations.