Affiliation:
1. State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
Abstract
Dimeric prodrugs have been investigated intensely as carrier-free drug self-delivery systems (DSDSs) in recent decades, and their stimuli-responsive drug release has usually been controlled by the conjugations between the drug molecules, including the stimuli (pH or redox) and responsive sensitivity. Here, an acid-triggered dimeric prodrug of doxorubicin (DOX) was synthesized by conjugating two DOX molecules with an acid-labile ketal linker. It possessed high drug content near the pure drug, while the premature drug leakage in blood circulation was efficiently suppressed. Furthermore, its aggregation structures were controlled by fabricating nanomedicines via different approaches, such as fast precipitation and slow self-assembly, to regulate the drug release performance. Such findings are expected to enable better anti-tumor efficacy with the desired drug release rate, beyond the molecular structure of the dimeric prodrug.