Quercetin Covalently Linked Lipid Nanoparticles: Multifaceted Killing Effect on Tumor Cells

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Hydrophobic drug encapsulation is a significant challenge in drug delivery.
• Developing effective nanoformulations is crucial for enhancing drug efficacy and overcoming resistance.

Purpose of the Study:

• To synthesize and characterize novel lipid nanoparticles (LNPs) for hydrophobic drug delivery.
• To investigate the tumor cell-killing mechanisms of these nanoformulations.
• To improve the delivery of hydrophobic drugs, specifically quercetin (Qu), for enhanced anti-cancer effects.

Main Methods:

• Covalent linkage of lipophilic quercetin (Qu) to glyceryl caprylate-caprate (Gcc) via disulfide bonds using 3,3'-dithiodipropionic acid (DTPA) to create Qu-SS-Gcc.
• Fabrication of Qu-SS-Gcc lipid nanoparticles (LNPs) using the solvent diffusion technique.
• Intracellular release studies using liquid chromatography, fluorescent quantitation, flow cytometry, and western blot to explore mechanisms in MCF-7/ADR cells.

Main Results:

• Qu-SS-Gcc LNPs effectively released Qu in MCF-7/ADR cells due to high concentrations of reduction molecules.
• Intracellular Qu levels were higher from Qu-SS-Gcc LNPs compared to free Qu.
• Qu-SS-Gcc LNPs demonstrated superior killing effects by inhibiting P-gp, arresting the cell cycle at G2, and inducing apoptosis and autophagy.

Conclusions:

• Qu-SS-Gcc LNPs facilitate massive accumulation of Qu in tumor cells, leading to multifaceted cell killing.
• The study provides a valuable reference for the delivery of hydrophobic drugs using prodrugs and nanoformulations.
• Autophagy's dual role as a survival or cell-killing mechanism depending on concentration was observed.