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Redox-Responsive Polymer–Drug Conjugates Based on Doxorubicin and Chitosan Oligosaccharide‑g‑stearic Acid for Cancer Therapy
journal contribution
posted on 2015-04-06, 00:00 authored by Yigang Su, Yingwen Hu, Yongzhong Du, Xuan Huang, Jiabei He, Jian You, Hong Yuan, Fuqiang HuHere,
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.