Details

Autor(en) / Beteiligte

• Su, Yigang
• Hu, Yingwen
• Du, Yongzhong
• Huang, Xuan
• He, Jiabei
• You, Jian
• Yuan, Hong
• Hu, Fuqiang

Titel

Redox-Responsive Polymer–Drug Conjugates Based on Doxorubicin and Chitosan Oligosaccharide‑g‑stearic Acid for Cancer Therapy

Ist Teil von

• Molecular pharmaceutics, 2015-04, Vol.12 (4), p.1193-1202

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.