Biomineralization-inspired dasatinib nanodrug with sequential infiltration for effective solid tumor treatment
Biomineralization-inspired dasatinib nanodrug with sequential infiltration for effective solid tumor treatment
复制标题
受生物矿化启发的达沙替尼纳米药物，具有连续浸润功能，可有效治疗实体瘤
DOI：
10.1016/j.biomaterials.2020.120481
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发表时间：
2021-01-01
期刊：
影响因子：
14
通讯作者：
Yin, Tingjie
中科院分区：
文献类型：
--
作者：
Liu, Yanhong;Li, Lingchao;Yin, Tingjie
The complex blood environment, heterogenic enhanced permeability and retention (EPR) effect, and dense matrix comprise the primary "leakage obstacles" impeding specific accumulation and penetration of nanodrugs against solid tumors, thus forming a key bottleneck for their clinical application. Herein, we present a biomineralization-inspired dasatinib (DAS) nanodrug (CIPHD/DAS) that sequentially permeates all of the abovementioned hindrances for efficient treatment of solid tumors. CIPHD/DAS exhibited a robust hybrid structure constructed from an iRGD-modified hyaluronic acid-deoxycholic acid organic core and a calcium phosphate mineral shell. In vitro and in vivo data demonstrated the mechanism of sequential tumoral infiltration was based on mineral-stiffened blood circulation with decreased premature drug leakage, iRGD-endowed tumor specific transendothelial transport for "first-order promotion of accumulation" and DAS-mediated restoration of fibrotic stromal homeostasis for "second-order promotion of penetration". Resultantly, CIPHD/DAS showed remarkable distal drug availability in desmoplastic 4T1/CAFs orthotropic mouse models and significantly suppressed tumor growth and metastasis. This optimized strategy with sequential permeabilization of the capital "leakage obstacles" validates a promising paradigm to conquer the "impaired delivery and penetration" associated bottleneck of nanodrugs in the clinical treatment of solid tumors.
