Fluorination Effects on the Drug Delivery Property of Cylindrical Polymer Brushes

Abstract

Fluorination has been widely applied to improving the properties of small-molecule drugs. However, relatively little is known about the effects of fluorination on the drug delivery property of nanomaterials. In this paper, we synthesized a fluoroalkane-modified cylindrical polymer brush (CPB) BCPB-F and an alkane-modified analogue BCPB-H. Doxorubicin (DOX) was used as a model drug and was loaded onto the CPBs through a pH-responsive acylhydrazone linkage. High drug loading and good water solubility were achieved. The in vitro and in vivo experiments suggested that fluorination played an important role in improving the cellular uptake, blood circulation, tissue permeability, and tumor targeting ability of CPBs. Due to these superiorities, the DOX-loaded BCPB-F exhibited excellent antitumor efficacy and eradicated the tumors of mice after five-dose treatments. The well-defined structures of the drug-free and drug-loaded CPBs guaranteed the accuracy of the results. This work demonstrates that fluorination is a promising strategy to improve the overall properties of nanomedicines.

Phenylboronic acid-modified nanoscale multi-arm polymers for tumor-targeted therapy

“…16,17 Typically, unimolecular micelles, water-soluble dendrimers and cylindrical polymer brushes can be considered as UPNs. [18][19][20] UPNs can overcome the shortcomings of polymeric nanoassemblies because their good stability and designable drug conjugation ensure controllable drug release, and their well-defined structures impart batch-to-batch reproducible biological properties. However, UPNs generally suffer from complicated synthesis procedures, especially those for dendrimers and cylindrical polymer brushes.…”

Divergent Generation of the Difluoroalkyl Radical and Difluorocarbene via Selective Cleavage of C–S Bonds of the Sulfox-CF2SO2Ph Reagent

“…The selective introduction of fluorine atoms or fluorinated moieties into organic molecules can often bring about profound changes in the latter’s physical and biological properties. For instance, the difluoromethyl (CF 2 H) and difluoroalkyl (CF 2 R, where R ≠ H) groups have found wide applications in pesticides, functional materials, and pharmaceuticals . The synthesis of difluoromethylated and difluoroalkylated compounds generally relies on the use of corresponding CF 2 H- and CF 2 R-transfer reagents, such as Si-based, Zn-based, P-based, I-based, and S-based difluoromethylation and difluoroalkylation reagents, among which the difluoromethyl sulfoximines and sulfones , have attracted a great deal of attention owing to their unique reactivity in organic synthesis.…”