Distinguishing the Cellular Transport of Folic Acid Conjugated Nano-Drugs among Different Cell Lines by Using Force Tracing Technique

Folic acid (FA) is a ligand that has been renowned for its strong binding to FA receptor (FR), and the robustness of the specific interaction has led to the generation of multitudinous tumor-targeted nano-drug delivery systems. However, selecting the appropriate FA targeted nano-drugs according to types of cancerous cells to achieve a high effect is critical. Understanding of how the drug is transported through the cell membrane and is delivered intracellularly is very important in screening ideal targeted nano-drugs for cancerous changes in different organs. Herein, by using a force tracing technique based on atomic force microscopy (AFM), the dynamic process of FA-polyamidoamine-Doxorubicin (FA-PAMAM-DOX) entry into different tumor cells (HeLa and A549) and normal cells (Vero) was monitored in real time. The cell membrane transport efficacy of FA-PAMAM-DOX in tumor cells with an FR high overexpression level (HeLa) and FR low overexpression level (A549) is analyzed, which is significantly higher than that in normal cells (Vero), especially for HeLa cells. Subsequently, the intracellular delivery efficiency of FA-PAMAM-DOX in different cell lines was measured by using fluorescence imaging and AFM-based nanoindentation techniques. This report will help to discover the cellular transport mechanism of nano-drugs and screen out optimal therapeutic nano-drugs for different types of tumors.