Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Research

Background:

• Lung cancer is a leading cause of cancer mortality globally.
• Novel therapeutic strategies are essential for effective lung cancer treatment.
• Aptamers (APTs) show promise for targeted cancer therapy, but their cellular uptake mechanisms require further investigation.

Purpose of the Study:

• To investigate the internalization mechanism of S15-aptamers into human non-small cell lung cancer A549 cells.
• To evaluate the specificity and binding affinity of aptamer-decorated quantum dots for A549 cells.
• To explore the potential of aptamer-mediated cellular uptake for overcoming cancer multidrug resistance.

Main Methods:

• Utilized quantum dots (QDs) functionalized with S15-aptamers (APTs) for targeted delivery.
• Assessed selective binding and internalization in A549 cells versus normal and other cancer cell lines (BEAS2B, HeLa, CaCo-2).
• Employed flow cytometry to determine the dissociation constant (Kd) and used endocytosis inhibitors to elucidate the uptake pathway.

Main Results:

• APT-decorated QDs demonstrated high specificity and selective uptake by A549 lung cancer cells.
• A low dissociation constant (Kd = 13.1 ± 1.6 nM) indicated strong binding affinity to A549 cells.
• Cellular uptake was confirmed to occur via clathrin-dependent receptor-mediated endocytosis.

Conclusions:

• S15-aptamer internalization into A549 cells occurs through a well-defined clathrin-dependent endocytic pathway.
• This specific cellular entry mechanism offers potential for developing targeted nanomedicines.
• The findings suggest a strategy to bypass multidrug resistance efflux pumps in cancer therapy.