Your browser doesn't support javascript.
loading
Biomineralization-inspired dasatinib nanodrug with sequential infiltration for effective solid tumor treatment.
Liu, Yanhong; Li, Lingchao; Liu, Jiyong; Yang, Mengnan; Wang, Honglan; Chu, Xuxin; Zhou, Jianping; Huo, Meirong; Yin, Tingjie.
Afiliación
  • Liu Y; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • Li L; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • Liu J; Department of pharmacy, Fudan University Shanghai Cancer Center, Shanghai, 200433, China.
  • Yang M; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • Wang H; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • Chu X; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • Zhou J; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: cpu_zhoujp@163.com.
  • Huo M; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: huomeirongcpu@163.com.
  • Yin T; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: cookey_89ytj@163.com.
Biomaterials ; 267: 120481, 2021 01.
Article en En | MEDLINE | ID: mdl-33189053
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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Neoplasias Límite: Animals Idioma: En Revista: Biomaterials Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Neoplasias Límite: Animals Idioma: En Revista: Biomaterials Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos