Dual Stimuli-Responsive Gemcitabine-Conjugated Alginate-Chitosan Nanoparticles for Triple-Negative Breast Cancer...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Gemcitabine (GEM) is effective against cancers but has poor pharmacokinetics.
• Improved drug delivery systems are needed to enhance GEM efficacy and reduce toxicity.

Purpose of the Study:

• To develop dual stimuli-responsive hybrid polymeric nanoparticles conjugating GEM using a chitosan alginate biopolymer.
• To enhance GEM's systemic exposure, stability, and therapeutic efficacy while minimizing toxicity for breast cancer treatment.

Main Methods:

• Chitosan alginate biopolymer was used to create hybrid polymeric nanoparticles conjugating GEM via hydrazone and disulfide linkers.
• Nanoparticles were characterized for physicochemical properties, stimuli-responsive drug release, and hemolysis.
• Therapeutic potential was assessed in breast cancer cell lines (4T1, MCF-7, MDA-MB-231) and in vivo using 4T1-Luc tumor-bearing mice.

Main Results:

• The developed Alg/Chi-GEM nanoparticles exhibited robust physicochemical properties and stimuli-responsive drug release.
• In vitro studies showed superior cellular uptake, enhanced cytotoxicity, and efficient apoptosis induction in breast cancer cells.
• In vivo studies demonstrated significant tumor growth inhibition with reduced toxicity compared to free GEM.

Conclusions:

• Dual stimuli-responsive Alg/Chi-GEM nanoparticles represent a promising nanomedicine for overcoming gemcitabine resistance.
• This nanoplatform offers a safer and more effective approach for enhancing breast cancer therapy.