Dual pH-Sensitive DOX-Conjugated Cyclodextrin-Core Star Nano-Copolymer Prodrugs

Herein this study reports dual pH-sensitive doxorubicin (DOX)-conjugated beta-cyclodextrincore star copolymers with tailoring properties such as direct water-solubility and stability prior to reaching target sites. For these purposes, three kinds of novel welldefined beta-cyclodextrin-core poly(2-(diethylamino) ethyl methacrylate-co-4-formylphenyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) star copolymers (CDstar- P(DEA-co-FPMA)-b-PPEGMA, SPDFP1-3) with different poly(ethylene glycol) methyl ether methacrylate contents are designed and synthesized by atom transfer radical polymerization (ATRP) strategy. 4-Formylphenyl methacrylate is introduced into the inner arm block of the star copolymers for conjugating DOX by imine bond formation. Interestingly, the DOXconjugated beta-cyclodextrin-core star copolymers not only can directly dissolve in aqueous buffer solution of pH 7.0 to form unimolecular micelles without any aid of organic solvent, but also exhibit strong pH-dependent DOX release. At normal pH 7.4 the DOX amount released is very small, whereas at pH 5.0 DOX can be released. By selecting SPDFP2-DOX as a representative, it is found that the SPDFP2-DOX micelles show less cytotoxicity compared to carrier-free DOX and can be internalized by HeLa cells. It is expected that the exploration can provide new strategy for preparing drug delivery system.