Preferential Delivery of BPM 31510 into Tumorigenic Cells Based on Biophysical Interactions

Abstract

Preferential drug delivery to cancer cells has remained elusive. Current approaches utilize ligand-receptor interactions or enhance vasculature in tumor area, but do not take into consideration the significant difference in organization and dynamics of tumorigenic cells surface compared to non- tumorigenic counterpart. It is extensively reported that tumorigenic cells have lower lateral packing density that also relates to their metastatic and invasive potential. Herein, we report a preliminary investigation on BPM 31510, a CoQ10 based lipid nanodispersion that demonstrate preferential incorporation into membranes with lower lateral packing density. We first employed lipid membranes at air-water interface with lower and higher packing densities as a mimic of tumorigenic and non-tumorigenic cell surfaces and injected BPM 31510 in aqueous sub-phase. We observed a decrease in BPM 31510 incorporation with an increase in lateral packing density of the membranes. Later, intracellular concentration of CoQ10 following treatment with BPM 31510 was compared in nine tumorigenic cells lines and five non-tumorigenic cell lines. The uptake of BPM 31510 was much higher in tumorigenic cells compared to non-tumorigenic cells. Data further suggest suggests that free energy related to addition of BPM 31510 into the cell surface is significantly lower in tumorigenic cells compared to non-tumorigenic counterpart. Overall, this work employ BPM 31510 as model system to demonstrate how preferential drug delivery into tumorigenic cell surface can be achieved by utilizing its lower lateral packing density compared to non-tumorigenic counterpart.