%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