1 research outputs found
Redox-Responsive Polymer–Drug Conjugates Based on Doxorubicin and Chitosan Oligosaccharide‑<i>g</i>‑stearic Acid for Cancer Therapy
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. <i>In vitro</i> 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 <i>in vivo</i>, which showed selectively accumulation in tumor
and reduced nonspecific accumulation in hearts. <i>In vivo</i> 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