Aptamers for Targeted Delivery: Current Challenges and Future Opportunities

Abstract

Aptamers are synthetic ssDNA/RNA molecules that are emerging as novel tools for the development of therapeutics, especially for targeted delivery. Aptamers are comparable to monoclonal antibodies, which are well-established therapeutic molecules, in terms of specificity and affinity to their target. The advantage of aptamers over antibodies includes their high stability, ease of synthesis, less batchto-batch variation, easy chemical modifications that allow different conjugation chemistries, small size for better tissue penetration and low immunogenicity. These advantages make aptamers an important tool for use in therapeutics for targeted delivery. However, aptamers do have some limitations that have hindered their widespread clinical use as a therapeutic agent. Some of their common limitations include serum stability, renal filtration and endocytic escape. Other limitations that are more specific to aptamers include lack of diversity in the aptamer library, nuclease susceptibility and claims of aptamer specificity as well. This book chapter sheds light on these challenges, and using examples, it explains the scientific advancements that have been achieved in overcoming these limitations. We will end this chapter by discussing the use of high-throughput technology, which is the only way of truly industrializing the aptamer technology akin to the development of small molecule drugs.

Investigation of Specific Targeting of Triptorelin-Conjugated Dextran-Coated Magnetite Nanoparticles as a Targeted Probe in GnRH+ Cancer Cells in MRI

“…e mechanism of triptorelin-based internalization gives rise to receptor-mediated endocytosis [17], resulting in efficient internalization of formulation into the GnRH-expressing cells.…”

“…Conjugation of SPIONs with tumor targeting moieties such as antibodies, aptamers, or peptides represents a promising platform for selective diagnosis of cancer biomarker/receptors and specific delivery of MRI agents. The specific binding of a peptide to its receptors (specific ligand-receptor interaction) which are overexpressed in cancer cells, resulting in efficient internalization of SPIONs into the cells based on receptor-mediated endocytosis (RME) [ 17 , 18 ]. Moreover, it possibly helps a delay in extravasations from tumor tissues, thereby increasing the residence time of MRI agents in the tumor site.…”

Machine-Perception Nanosensor Platform to Detect Cancer Biomarkers

“…Eleven DNA sequences ((AT)11, (AT)15, (AT)20, (GT)12, (ATT)4, (TCT)5, T3C3T3C3T3, C3T9C3, C3T3C9, CT2C3T2C, and (AC)15) were chosen because many of them are recognition sequences of specific SWCNT chiralities, which suggest ordered wrapping on their surface, while others confer some degree of specificity to proteins or other analytes. [47][48][49][50] Twelve semiconducting SWCNT species present in the HiPCO preparation ((6,5), (8,4), (10,3), (7,5), (7,6), (8,3), (9,5), (9,4), (8,6), (8,7), (10,2), and (9,7)) were evaluated due to their high concentrations in the sample and bright photoluminescence in the serum/water optical window of 900-1400 nm (Fig. S1A, B).…”

“…Current biomolecular identification methodologies rely heavily on one-to-one recognition via specific proteins and nucleic acids such as antibodies, peptides, and aptamers to bind analytes. [1][2][3][4][5] However, the development of highly sensitive and specific binding moieties in a quantity sufficient to detect target molecules with one-to-one recognition has multiple challenges that delay the development of a robust, versatile, and cost-effective platform for multiple analyte detection.…”

Targeted delivery, drug release strategies, and toxicity study of polymeric drug nanocarriers

“…This is due to their small size, resulting in better tissue penetration, reduced immunogenicity, and ease of synthesis. However, there are some issues with aptamers too, such as serum stability and renal filtration 39 . Besides, there are a lot of small molecules utilized as ligands; however, they are in narrow usage because not all cancerous cells overexpressing the related receptors on their surface.…”