Supramolecular polymeric prodrug micelles for efficient anticancer drug delivery†
c
and
Weipu
Zhu
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Abstract
Polymeric prodrugs have attracted great interest in the field of anticancer drug delivery owing to their integrated advantages of prodrugs and nanoparticles. However, the ambiguous chemical composition of polymeric prodrugs is still a major obstacle to their clinical applications. In this study, an amphiphilic poly(ethylene glycol) derivative with multiple thiols was first synthesized on a large scale through the melt co-polycondensation of oligo(ethylene glycol), 1,4-butanediol and mercaptosuccinic acid. Then an adamantane modified doxorubicin (DOX) with a pH-sensitive hydrazone bond and a β-cyclodextrin derivative with multiple acryloyls were precisely synthesized. Finally, novel supramolecular polymeric prodrug (SPP) micelles with a precise drug molecular structure and drug loading content were facilely prepared using the above three components via simultaneous self-assembly, a thiol–ene “click” reaction and a host–guest supramolecular interaction in water. The resultant pH-sensitive SPP micelles with a stable core-crosslinked structure and strong drug “bonding” show long blood circulation time, effective cellular uptake and fast DOX release in tumor cells, which significantly improved the antitumor efficacy and security compared with free DOX. This work established a promising drug delivery platform for cancer chemotherapy.
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