**3. Strategies for prolonging the half-life of aptamers**

Due to their quick elimination via renal filtration, tiny aptamers continue to provide a barrier for renal clearance (**Figure 4**). To solve this, several techniques, including the attachment of cholesterol, PEG, proteins, liposomes, and other materials, have been reported. PEGylation, in particular, is a well-established and commonly utilized technique for prolonging medication half-life. Other approaches, such as lipid nanoparticle delivery systems and attachment to bioactive natural proteins, have also been used to improve the metabolic stability and pharmacokinetic features of therapeutic nucleic acid aptamers. Alternative PEGylation approaches, such as employing long-half-life proteins and low molecular weight coupling agents, have also been investigated to extend the half-life of aptamers. These methodologies may be adapted

to specific aptamer applications and therapeutic purposes, allowing for the creation of aptamers with increased stability, bioavailability, and circulation half-life.
