Uptake mechanisms of cell-internalizing nucleic acid aptamers for applications as pharmacological agents

Nucleic acid aptamers, also regarded as chemical antibodies, show potential as targeted therapeutic and delivery agents since they possess unique advantages over antibodies. Generated by an iterative selection and amplification process from oligonucleotide libraries using cultured cells, the aptamers bind to their target molecules expressed on the cell surface. Excitingly, most aptamers also demonstrate a cell-internalizing property in native living cells, allowing them to directly enter the cells via endocytosis depending on the target. In this review, we discuss selection methods in generating cell-internalizing aptamers via a cell-based selection process, along with their challenges and optimization strategies. We highlight the cellular uptake routes adopted by the aptamers and also their intracellular fate after the uptake, to give an overview of their mechanism of action for applications as promising pharmacological agents.

Automated summary

Nucleic acid aptamers, also known as chemical antibodies, show promise as targeted therapeutic and delivery agents due to unique advantages over antibodies. Most aptamers can be internalized by cells and enter cells directly, which is important for their potential as pharmacological agents. Understanding selection methods, cellular uptake pathways, and intracellular fates of aptamers is crucial for their applications in medicine.