Molecular aptamers for drug delivery

Abstract

The active targeting of drugs in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology with widespread applications in medicine, including the treatment of cancers. Aptamers, with properties such as high affinity and specificity to their targets, easy chemical synthesis and modification, as well as rapid tissue penetration, have become attractive molecules in diagnostics and therapeutics. They rival and, in some cases, surpass other molecular probes, such as antibodies. In this review, we highlight the recent progress in aptamer-mediated delivery for therapeutics and disease-targeting based on aptamer integration with a variety of nanomaterials, such as gold nanorods, DNA-micelles, DNA-hydrogels and carbon nanotubes.

Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics

“…A theranostic (4) platform with targeted and efficient drug transport would solve these problems, and, by its programmability, DNA nanotechnology has been used for the rational assembly of one-, two-, and three-dimensional nanostructures (5)(6)(7)(8), which have been further studied for biomedical applications, including the passive targeted transport of theranostic agents (9)(10)(11)(12)(13)(14)(15)(16)(17). In addition, aptamers, as specific recognition elements, have been studied for active targeted transport of conventional chemotherapeutic drugs (11,12,(18)(19)(20)(21). Nucleic acid aptamers are single-stranded oligonucleotides with unique intramolecular conformations and specific recognition abilities to cognate targets, including mammalian cancer cells (22)(23)(24)(25)(26).…”

“…Nucleic acid aptamers are single-stranded oligonucleotides with unique intramolecular conformations and specific recognition abilities to cognate targets, including mammalian cancer cells (22)(23)(24)(25)(26). Recent biotechnological advancements have led to a variety of targeted drug transport (TDT) strategies based on aptamer-drug conjugates or aptamer-nanomaterial assemblies (11,12,(18)(19)(20)(21)27). However, these strategies have unique limitations that could hamper the transition to clinical application, including (i) complicated design, laborious and uneconomical bulky preparation of myriad ssDNA as building blocks to construct sophisticated nucleic acid-based nanomaterials, or laborious and inefficient preparation of aptamer-drug conjugates (9,11,14,15,17,18); (ii) limited drug payload capacity and the attendant high cost, hampering production scale-up (9,11,14,15,17,18,20,27); (iii) poor biodegradability, causing chronic accumulation of nanomaterials in vivo (28,29); and (iv) limited universality by the requirement of specific aptamer for drug loading (20).…”

Targeted Nanoparticles for Cancer Therapy

“…However, development of a technique called 'in vitro selection' or Systematic Evolution of Ligands by Exponential Enrichment (SELEX) has allowed the rapid and selective production of aptamers. Briefly, the SELEX method starts with a random library of 1013-1016 single-stranded DNA or RNA and uses an iterative process that specifically amplifies sequences that have high binding affinity to the target molecules [46][47]. Although many complex forms of SELEX exist, there are two basic forms of SELEX (Cell-SELEX and Automated SELEX) [41].…”

“…Aptamers can be designed as targeting ligands, and can differentiate diseased cells from healthy cells, thus enabling the selective delivery of therapeutic compounds to target cells [41,47]. A large number of aptamers have been raised against cancer-associated antigens such us AS1411 aptamer for targeting nucleolin protein, which is highly expressed in the membrane of cancer cells [48][49], aptamers CPG 7909 and IMO 2055, that target Toll-like receptor 9 (TLR9), which is expressed by certain immune cells, TD05 aptamer, which was selected for the Burkitt's lymphoma Ramos cell line [47], Sgc8c aptamer which targets leukemia biomarker protein tyrosine kinase-7 (PTK7) [46,50] and can recognize target leukemia cells, DNA aptamers to leukemic lymphoid (CEM) cells [46], and fruoropyrimidine RNA aptamers which target Prostate-specific membrane antigen (PSMA) [51] for targeting prostate cancer.…”

“…A large number of aptamers have been raised against cancer-associated antigens such us AS1411 aptamer for targeting nucleolin protein, which is highly expressed in the membrane of cancer cells [48][49], aptamers CPG 7909 and IMO 2055, that target Toll-like receptor 9 (TLR9), which is expressed by certain immune cells, TD05 aptamer, which was selected for the Burkitt's lymphoma Ramos cell line [47], Sgc8c aptamer which targets leukemia biomarker protein tyrosine kinase-7 (PTK7) [46,50] and can recognize target leukemia cells, DNA aptamers to leukemic lymphoid (CEM) cells [46], and fruoropyrimidine RNA aptamers which target Prostate-specific membrane antigen (PSMA) [51] for targeting prostate cancer. And also another aptamers against antigens such as pigpen [52] for targeting the tumor microvasculature, or mucin 1 (MUC1) [53] for targeting various epithelial neoplasms that upregulate MUC1, whose expression has been associated with carcinomas.…”