%0 Journal Article %A Su, Yigang %A Hu, Yingwen %A Du, Yongzhong %A Huang, Xuan %A He, Jiabei %A You, Jian %A Yuan, Hong %A Hu, Fuqiang %D 2015 %T Redox-Responsive Polymer–Drug Conjugates Based on Doxorubicin and Chitosan Oligosaccharide‑g‑stearic Acid for Cancer Therapy %U https://acs.figshare.com/articles/journal_contribution/Redox_Responsive_Polymer_Drug_Conjugates_Based_on_Doxorubicin_and_Chitosan_Oligosaccharide_i_g_i_stearic_Acid_for_Cancer_Therapy/2180083 %R 10.1021/mp500710x.s001 %2 https://acs.figshare.com/ndownloader/files/3814006 %K polymer %K vivo antitumor studies %K DOX %K conjugate %K disulfide linkers %K antitumor activity tests %K micelle %K drug delivery system %K reductive intracellular environments %K accumulation %X Here, a biodegradable polymer–drug conjugate of doxorubicin (DOX) conjugated with a stearic acid-grafted chitosan oligosaccharide (CSO-SA) was synthesized via disulfide linkers. The obtained polymer–drug conjugate DOX-SS-CSO-SA could self-assemble into nanosized micelles in aqueous medium with a low critical micelle concentration. The size of the micelles was 62.8 nm with a narrow size distribution. In reducing environments, the DOX-SS-CSO-SA could rapidly disassemble result from the cleavage of the disulfide linkers and release the DOX. DOX-SS-CSO-SA had high efficiency for cellular uptake and rapidly released DOX in reductive intracellular environments. In vitro antitumor activity tests showed that the DOX-SS-CSO-SA had higher cytotoxicity against DOX-resistant cells than free DOX, with reversal ability up to 34.8-fold. DOX-SS-CSO-SA altered the drug distribution in vivo, which showed selectively accumulation in tumor and reduced nonspecific accumulation in hearts. In vivo antitumor studies demonstrated that DOX-SS-CSO-SA showed efficient suppression on tumor growth and relieved the DOX-induced cardiac injury. Therefore, DOX-SS-CSO-SA is a potential drug delivery system for safe and effective cancer therapy. %I ACS Publications