As a leading service provider focused on drug development, BOC Sciences has been supporting customers at the forefront of drug conjugation. Building drug conjugates facilitates the selective delivery of toxic therapeutic cargos to diseased cells. Among them, nucleic acid aptamers are one of the delivery systems that have received the most attention. We provide aptamer drug conjugation services to meet your unique project needs.
Because they are subject to nuclease degradation and their small size makes them susceptible to renal filtration, aptamers usually require chemical modification. Aptamers are short, single-stranded DNA or RNA oligonucleotides whose biological stability and binding affinity can be enhanced by introducing modifications to their sugar units, nucleobases, or phosphate backbones. Common methods for aptamer conjugation include thiol-maleimide, carbodiimide, oxidative coupling, avidin-biotin coupling, and click chemistry.
Aptamers have been used in drug delivery systems carrying various types of drug cargos. BOC Sciences has the expertise in aptamer conjugation, including conjugating aptamers to therapeutic agents creates aptamer drug conjugates (ApDCs), enabling the precise delivery of drugs to specific cells or tissues and minimizing off-target effects.
Nucleic acid aptamers, also known as chemical antibodies, has a unique three-dimensional structure allowing it to bind to a molecular target through secondary or tertiary conformation, served as potential drug-delivery vehicles. The targets of aptamers range from small molecules and proteins to intact cells.
Advantages of aptamers served as targeting ligands:
| Aptamer Name | Targets | Aptamer Name | Targets | Aptamer Name | Targets |
| CD4 | RORγt | TR14 | hTfR2 | S30 | CD33 |
| sgc8 | PTK7 | AP-1 | CD133 | GL44 | U-87 MG |
| Zy1 | SMMC-7721 | AptABCG2 | ABCG2 | AS1411 | Nucleolin |
| SL₂-B | Hep G2 | APTA12 | Nucleolin | apt4-1BB | 4-1BB |
| RNV-L7 | LDL-R | aptPD-L1 | PD-L1 | MP7 | PD-1 |
| G12msi | GPC3 | AptCTLA-4 | CTLA-4 | TIM3Apt | TIM-3 |
| CD28Apt7 | B16 | MUC-1 | MCF-7 | Apt1, Apt2, Apt4, Apt5 | LAG3 |
| P19 | PANC-1 | CL4 | EGFR | RCA II | CD40 |
Table 1. Examples of aptamers selected with potential for targeted therapy (Liu, 2022)
The process of developing aptamers is known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). During SELEX, a random pool of nucleic acid sequences is exposed to the target molecule, and those sequences that bind to the target are selectively enriched through iterative rounds of selection, amplification, and isolation. This iterative process leads to the identification of specific aptamer sequences that exhibit high affinity and specificity for the target.
In the context of drug development, ApDCs have been developed for targeted therapy. An ApDC typically consists of three molecular parts: a ligand (aptamer), a linker, and a warhead (drug). In these conjugates, aptamers specifically recognize diseases-associated biomarkers to deliver conjugated drugs to target cells or/and tissues. The chemical stability and simplicity of chemical modification of aptamers allow these to be easily combined with many warheads, such as chemotherapeutics, nucleic acids, proteins, photosensitizers, etc.
Fig 1. Aptamer conjugation with drug, antibody, or RNA (Chen, 2022)
| Aptamer-Drug Conjugates | Aptamers | Therapeutic Cargoes |
| Aptamer-chemotherapeutic conjugates | sgc8, AS1411, A10, APT | Chemotherapeutics |
| Aptamer-nucleic acid conjugates | A10, CH6, Anti-gp120 | siRNA |
| Aptamer-peptide conjugates | GS24 | Peptide |
| Aptamer-photosensitizer conjugates | AIR-3A, sgc8, TD05, AS1411 | Photosensitizers |
| Aptamer-photothermal agent conjugates | sgc8 | Photothermal agents |
Table 2. Examples of aptamer-drug conjugates
Combined with aptamer, the diagnosis and treatment of diseases can effectively avoid the problems of low diagnostic sensitivity in vivo, large side effects of drugs, difficult tumor monitoring and so on. With the continuous development of aptamers, ApDC with different target sites are more and more widely used. ApDCs are used for targeting drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy and photothermal therapy for the treatment of various cancers such as liver, ovarian, skin, prostate, breast, pancreatic and anaplastic thyroid cancers, as well as acquired immunodeficiency syndrome. In addition, aptamer conjugates can be extended to other types of metal-organic framework (MOF) nanomaterials, and conjugates with targeted therapeutic and imaging capabilities can be developed for cancer cell detection and imaging.
Aptamers have the ability to bind with high specificity to their target molecules, which enhances the precision of drug delivery. By attaching drugs to aptamers, the conjugates can selectively target cells or biomolecules, improving the efficiency of molecular research while reducing off-target effects that may arise in conventional drug delivery systems.
Aptamer-drug conjugates offer multiple benefits in research, including improved selectivity, enhanced stability, and better control over drug activity. They are ideal for applications requiring targeted delivery and can be customized for different molecular systems, enabling more accurate studies of drug interactions and delivery mechanisms.
Aptamer-drug conjugation involves linking aptamers, short oligonucleotide sequences with high specificity, to drug molecules. The aptamers provide a targeting mechanism that directs the drug to a specific molecular site. This conjugation enhances the drug's bioavailability and stability, making it highly effective for targeted molecular studies and experimental applications.
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