Multivalent cyclic template-directed synthesis of polycyclodextrin-based nanocarriers for enhanced chemotherapy

Nanocarriers with reversibly crosslinked structures provide one solution to the in vivo stability versus high therapeutic efficiency dilemma, however, generally suffer from a diluted condition-required synthetic approach for crosslinking. To address this issue, we reported herein multivalent cyclic template-directed synthesis of polycyclodextrin (polyCD)-based nanocarriers. The adopted multivalent cyclic template with great stability and steric hindrance resulted in a relatively high preparation concentration of 1.0 mg/mL for crosslinking. The synthesized dual-redox responsive polyCD-based crosslinked micelles showed enhanced colloidal stability, a high drug loading content (DLC) of 17.8% for doxorubicin (DOX), and intracellular complete destruction for promoted DOX release with enhanced anticancer efficiency in vivo. This study therefore not only reported the use of a multivalent cyclic polymer as a novel template for the production of polyCDs-based crosslinked micelles and ring-like colloids at a relatively high concentration, but also demonstrated great potential of the developed (polyCD)-based nanocarriers for enhanced chemotherapy.