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Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer.
Zhang, Guiyang; Jiang, Bo; Wu, Chunyong; Liu, Yanfeng; He, Yidan; Huang, Xin; Chen, Wei; Xi, Kai; Guo, Hongqian; Zhao, Xiaozhi; Jia, Xudong.
Afiliación
  • Zhang G; School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu 210023, China. xikai@nju.edu.cn jiaxd@nju.edu.cn and Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
  • Jiang B; Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, P. R. China. dr.ghq@nju.edu.cn zhaozx@nju.edu.cn.
  • Wu C; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
  • Liu Y; School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu 210023, China. xikai@nju.edu.cn jiaxd@nju.edu.cn.
  • He Y; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
  • Huang X; School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu 210023, China. xikai@nju.edu.cn jiaxd@nju.edu.cn.
  • Chen W; Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, P. R. China. dr.ghq@nju.edu.cn zhaozx@nju.edu.cn.
  • Xi K; School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu 210023, China. xikai@nju.edu.cn jiaxd@nju.edu.cn.
  • Guo H; Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, P. R. China. dr.ghq@nju.edu.cn zhaozx@nju.edu.cn.
  • Zhao X; Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, P. R. China. dr.ghq@nju.edu.cn zhaozx@nju.edu.cn.
  • Jia X; School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu 210023, China. xikai@nju.edu.cn jiaxd@nju.edu.cn.
J Mater Chem B ; 8(20): 4475-4488, 2020 05 27.
Article en En | MEDLINE | ID: mdl-32365151
ABSTRACT
Effective treatment of brain metastases is hindered by the blood-brain barrier (BBB) and the rapid development of resistance to drug therapy. Moreover, the clinical application of general formulations is hampered by biological barriers and biological elimination. To tackle this challenge, we report a feasible approach for the assembly of polymer-covalent organic framework (COF) nanocomposites into 150 nm thin platelets as a drug delivery vehicle for enhanced retention in brain tumours. Using intravital imaging, we demonstrate that these polymer-COF nanocomposites are able to traverse the BBB in mice and achieve direct tumour accumulation in intracranial orthotopic models of brain metastasis from renal cancer (BMRC). These nanocomposites can target brain tumour cells and respond to tumour microenvironmental characteristics, including acidic and redox conditions. Intracranial tumour acidity triggers the breakdown of the nanoassemblies to polymer-COF nanocomposites due to the presence of borate bonds. Furthermore, in vivo studies on the nanocomposites showed enhanced brain tumour-targeting efficiency and therapeutic effects compared to those of free-drug dosing. Mice treated with drug-loaded polymer-COF nanocomposites also show protection from systemic drug toxicity and improved survival, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to BMRC and other central nervous system (CNS) tumours.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Polímeros / Neoplasias Encefálicas / Barrera Hematoencefálica / Nanocompuestos / Estructuras Metalorgánicas / Neoplasias Renales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Mater Chem B Año: 2020 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Polímeros / Neoplasias Encefálicas / Barrera Hematoencefálica / Nanocompuestos / Estructuras Metalorgánicas / Neoplasias Renales / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Mater Chem B Año: 2020 Tipo del documento: Article País de afiliación: China