Polymer-coated echogenic lipid nanoparticles with dual release triggers

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Lipid nanoparticles (LNPs) are effective drug carriers, but slow passive release limits their therapeutic potential.
• Controlled and triggered release mechanisms are needed to improve LNP efficacy at target sites.

Purpose of the Study:

• To develop polymer-coated, echogenic LNPs for triggered drug release.
• To investigate redox-triggered release in the cell cytoplasm.
• To evaluate the synergistic effect of ultrasound on drug release and therapeutic efficacy.

Main Methods:

• Synthesized polymer-coated, echogenic LNPs using a disulfide cross-linker.
• Loaded nanoparticles with doxorubicin and conjugated with folic acid for targeted delivery.
• Assessed drug release triggered by glutathione (cytosolic and plasma concentrations).
• Investigated the effect of diagnostic frequency ultrasound (3 MHz) on drug release kinetics.
• Evaluated nanoparticle uptake and cytotoxicity in folate receptor-overexpressing cancer cells.

Main Results:

• LNPs demonstrated significant drug release (76%) triggered by cytosolic glutathione concentrations.
• Plasma concentrations of glutathione did not induce substantial drug release, indicating target specificity.
• Ultrasound application (3 MHz, 2 min) combined with the reducing agent enhanced release to 96%.
• Folic acid-conjugated nanoparticles showed increased uptake and cytotoxicity in targeted cancer cells.

Conclusions:

• Developed LNPs offer a redox- and ultrasound-responsive platform for controlled drug release.
• The combination of redox triggering and ultrasound enhances therapeutic payload delivery.
• These multimodal nanocarriers hold promise for targeted cancer therapy and simultaneous ultrasound imaging.