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Novel dual redox/pH-sensitive star-like amphiphilic sucrose-oligo(butyl fumarate) (thioglycolic acid conjugate)–SS–poly(ethylene glycol) (Suc-OBF(TGA)–SS–PEG) copolymers and their self-assembled micelles were prepared and utilized for intracellular doxorubicin delivery. Importance of changing the hydrophobic chain length on micelles properties was investigated. Results showed that the micelles with longer hydrophobic chain exhibited smaller size and were more stable in aqueous solution. The redox and pH sensitivity of the micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic light scattering and the change of micellar morphology observed by scanning electron microscope. The micelles display a decent doxorubicin loading capacity. In vitro release studies showed that only 14.3% doxorubicin was released from doxorubicin-loaded micelles under physiological conditions in 30 h. The release of doxorubicin was accelerated at pH 5.5 or in the presence of 10 mM glutathione at pH 7.4 (46.9% and 76.9% of doxorubicin was released, respectively, in 30 h). The doxorubicin release was further expedited under pH 5.5 and 10 mM GSH conditions (91.4%). Suc-OBF(TGA)–SS–PEG micelles displayed no cytotoxicity toward HDF cells. MTT assays indicated that doxorubicin-loaded micelles had good cytotoxicity against MCF-7 cells. This work suggested that star-like amphiphilic Suc-OBF(TGA)–SS–PEG copolymer micelles may provide a promising platform for delivering doxorubicin and other hydrophobic anticancer drugs.

To overcome the problems associated with the use of doxorubicin (DOX), such as low solubility, high toxicity, and side effects, a redox and pH-sensitive drug delivery system based on a star-like copolymer of folate-modified poly (ethylene glycol) (PEG) and biodegradable castor oil was developed. Redox-sensitive disulfide linkage and pH-sensitive imine linkage were incorporated in the backbone of the star-like copolymer, which self-assembled into stable micelles with small particle size (91.67 nm), narrow size distribution, and low CMC value (2.7 mg/L). The disassembly behaviors of the micelles when exposed to endolysosomal pH of 5.5 and a high concentration of GSH were evaluated by scanning electron microscope from the changes of micellar morphology. The micelles were used to load DOX into the hydrophobic core. Drug loading capacity (DLC) and drug loading efficiency (DLE) were calculated to be 15.93% and 96.13%, respectively. In vitro release studies showed that DOX release from micelles followed a redox and pH-triggered manner. The introduction of dual trigger further expedited DOX release. In vitro cytotoxicity of the copolymer against HDF cells was investigated. The star-like copolymer showed no toxicity. While the DOX-loaded micelles suggested enhanced cytotoxicity against HeLa cells. These results indicated that these redox and pH-sensitive micelles have the potential as a nanocarrier for DOX and other hydrophobic anti-cancer drugs.