Targeting autophagy in triple negative breast cancer using chloroquine diphosphate loaded solid lipid nanoparticles: a nano formulation-based approach

Abstract

Triple-negative breast cancer (TNBC), a highly aggressive form of cancer, is characterized by the absence of estrogen, progesterone, and HER2 receptors. The absence of these receptors leads to reduced efficiency of targeted therapies. Autophagy, a survival mechanism in cancer cells, contributes to tumor progression and chemoresistance. Chloroquine diphosphate inhibits autophagy by disturbing lysosomal function, but it is clinically restricted due to poor solubility and non-specific toxicity. Solid lipid nanoparticles provide an improved drug delivery system for chloroquine diphosphate to increase its bioavailability and targeted action. The research aims to develop and evaluate chloroquine diphosphate-loaded solid lipid nanoparticles (CQD-SLNs) for increased suppression of autophagy and cytotoxicity in triple-negative breast cancer cells. CQD-SLNs were prepared by using solvent emulsification and evaporation method. It was characterized for particle size and stability. Cytotoxicity against TNBC cells was assessed via MTT assay, while cell migration was determined in the scratch (wound healing) assay. The results demonstrated that both cell viability and migration inhibition occurred in a dose-dependent manner, with concentrations above 0.075 μM significantly inhibiting wound closure when compared to control, demonstrating that CQD-SLNs can effectively inhibit cancer cell migration. This study indicates that SLNs enhance CQD's therapeutic potential via improved drug delivery, reduced cell migration, and inhibition of autophagy pathways. This drug delivery strategy gives a strong promise for inducing an efficient therapy using nanocarrier-based approaches for aggressive breast cancers like TNBC.