A pH-sensitive nano drug delivery system of doxorubicin-conjugated amphiphilic polyrotaxane-based block copolymers

A pH-sensitive nano antitumor drug delivery system was prepared by conjugating doxorubicin (DOX) to amphiphilic polyrotaxane (PR)-based block copolymers through a pH-sensitive cis-aconityl moiety. The resulting polymer-drug conjugates were able to self-assemble into polymeric micelles in an aqueous solution with diameters varying from 297 nm to 178 nm after the conjugation as evidenced by DLS measurements. The pH-sensitive cis-aconityl linkage provided a controlled and sustained release of DOX over a period of more than 5 days in an acidic environment mimicking the tumor microenvironment, and a negligible amount of release in an environment with physiological pH. The nanoparticles had lower cytotoxicity than the free drug and can efficiently transfer and release the drug into HeLa cells. With these promising properties, the PR-based block copolymers have the potential to be carriers for the controlled release of antitumor drugs.