Ditelluride-bridged, ROS-responsive nanoparticles based on carboxymethyl chitosan for potentiating doxorubicin...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Conventional chemotherapy faces challenges with systemic toxicity and poor drug targeting.
• Stimuli-responsive carriers are needed for sensitive drug release in pathological tissues with low reactive oxygen species (ROS).

Purpose of the Study:

• To develop and evaluate ditelluride-bridged carboxymethyl chitosan nanoparticles (DTeC NPs) for ROS-triggered doxorubicin (DOX) release.
• To compare the efficacy of DTeC NPs with disulfide-crosslinked nanoparticles (DSC NPs) as a control.

Main Methods:

• Fabrication of DTeC NPs and DSC NPs with uniform size (~200 nm) and high drug loading (~25%).
• Assessment of DOX release kinetics in response to hydrogen peroxide (H2O2) to mimic ROS levels.
• In vitro evaluation of cellular uptake and cytotoxicity in HepG2 and H22 cancer cell lines.
• In vivo assessment of tumor growth inhibition (TGI) in H22 tumor-bearing mice.

Main Results:

• DTeC NPs demonstrated significantly accelerated degradation and DOX release (98.1% in 48 hours at 100 μM H2O2).
• DTeC/DOX NPs enhanced cellular uptake and exhibited superior cytotoxicity against HepG2 and H22 cells compared to DSC/DOX NPs.
• In vivo studies showed DTeC/DOX NPs achieved a TGI rate of 72.29%, outperforming free DOX and DSC/DOX NPs.

Conclusions:

• The ditelluride-crosslinking strategy provides a highly sensitive platform for ROS-triggered drug delivery.
• DTeC NPs show significant potential for improving the precision and therapeutic efficacy of cancer chemotherapy.
• This approach offers a promising advancement in nanomedicine for targeted cancer treatment.