Boronate-dextran: an acid-responsive biodegradable polymer for drug delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Stimuli-responsive drug carriers offer targeted delivery of bioactive materials.
• Acid-responsive carriers are crucial for releasing drugs in acidic tumor microenvironments or intracellular compartments.

Purpose of the Study:

• To develop acid-responsive nanoparticles using functionalized dextran for drug delivery.
• To investigate the pH-responsive drug release capabilities of these nanoparticles.

Main Methods:

• Functionalization of dextran's vicinal diols with hydrophobic boronate esters to create boronate dextran (B-Dex) polymer nanoparticles.
• Encapsulation of the hydrophobic anticancer drug doxorubicin.
• Assessment of particle degradation and drug release at different pH levels (pH 5.0 vs. pH 7.4) using dynamic light scattering and UV/Vis spectroscopy.
• In vitro toxicity and cellular uptake studies in Hela cells.

Main Results:

• Boronate dextran (B-Dex) spontaneously forms acid-responsive nanoparticles in water.
• Particles demonstrate significantly increased degradation and doxorubicin release at pH 5.0 compared to pH 7.4.
• Empty B-Dex nanoparticles show no toxicity, while doxorubicin-loaded nanoparticles exhibit comparable toxicity to free doxorubicin.
• 100% cellular uptake of doxorubicin-loaded B-Dex nanoparticles observed in Hela cells, with preferential cytoplasmic accumulation.

Conclusions:

• Boronate dextran nanoparticles provide an effective platform for pH-responsive, targeted drug delivery.
• The acid-responsive nature of B-Dex nanoparticles facilitates controlled drug release in acidic conditions.
• These nanoparticles show potential for enhanced cancer therapy due to efficient cellular uptake and targeted drug release.