The assembly modules deformation strategy improved the chemical stability and self-assembly stability of docetaxel prodrugs nanoassemblies

Abstract

The self-assembly prodrugs usually consist of drug modules, activation modules, and assembly modules. The selection of suitable modules to construct prodrug nanoassemblies with self-assembly stability and intelligent activation is still a challenge. As a common assembly module, oleic acid can provide a driving force and steric hindrance for prodrugs self-assembly. However, unsaturated double bond of oleic acid is easily oxidized to affect its chemical stability. Herein, two docetaxel (DTX) prodrugs were designed using disulfide bonds as activation modules and two different fatty acids (isostearic acid and oleic acid) as assembly modules, respectively. Compared with oleic acid, isostearic acid has the advantage of higher chemical stability. At the same time, the terminal propyl structure of isostearic acid makes up for the steric hindrance without double bond. Overall, this structural deformation improved the self-assembly ability and chemical stability of the prodrug nanoassemblies, thus balancing the effectiveness and safety of the prodrugs. Our findings reveal the importance of the assembly modules and provide a guidance for the rational design of prodrug nanoassemblies.