Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 20, 2020
Previous Article Next Article

Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer

Author affiliations

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.

Graphical abstract: Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer

Back to tab navigation

Supplementary files

Article information


Submitted
16 Mar 2020
Accepted
15 Apr 2020
First published
16 Apr 2020

J. Mater. Chem. B, 2020,8, 4475-4488
Article type
Paper

Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer

G. Zhang, B. Jiang, C. Wu, Y. Liu, Y. He, X. Huang, W. Chen, K. Xi, H. Guo, X. Zhao and X. Jia, J. Mater. Chem. B, 2020, 8, 4475
DOI: 10.1039/D0TB00724B

Social activity

Search articles by author

Spotlight

Advertisements