Aptamers: an emerging navigation tool of therapeutic agents for targeted cancer therapy

Yang, Chang; Jiang, Yu; Hao, Sai Heng; Yan, Xinghong; Hong, Dongsheng; Naranmandura, Hua

doi:10.1039/d1tb02098f

Cited by 28 publications

(18 citation statements)

References 120 publications

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“…For example, pegaptanib, which was the first aptamer developed for wet age-related macular degeneration, was approved by the FDA, EMA, and PMDA in 2004, 2006, and 2008, respectively (50). Similarly, three newly generated aptamers-namely, AS1411, NOX-A12, and AGRO100-are currently in clinical trial for tumor therapeutics (51). These advances indicate the promising prospects for aptamers as therapeutic vehicles for certain troublesome diseases, including RA.…”

Section: Discussionmentioning

confidence: 99%

Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis

et al. 2022

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Connective tissue growth factor (CTGF) has been recently acknowledged as an ideal biomarker in the early disease course, participating in the pathogenesis of pannus formation in rheumatoid arthritis (RA). However, existing approaches for the detection of or antagonist targeting CTGF are either lacking or unsatisfactory in the diagnosis and treatment of RA. To address this, we synthesized and screened high-affinity single-stranded DNA aptamers targeting CTGF through a protein-based SELEX procedure. The structurally optimized variant AptW2-1-39-PEG was characterized thoroughly for its high-affinity (KD 7.86 nM), sensitivity (minimum protein binding concentration, 2 ng), specificity (negative binding to other biomarkers of RA), and stability (viability-maintaining duration in human serum, 48 h) properties using various biochemical and biophysical assays. Importantly, we showed the antiproliferative and antiangiogenic activities of the aptamers obtained using functional experiments and further verified the therapeutic effect of the aptamers on joint injury and inflammatory response in collagen-induced arthritis (CIA) mice, thus advancing this study into actual therapeutic application. Furthermore, we revealed that the binding within AptW2-1-39-PEG/CTGF was mediated by the thrombospondin 1 (TSP1) domain of CTGF using robust bioinformatics tools together with immunofluorescence. In conclusion, our results revealed a novel aptamer that holds promise as an additive or alternative approach for CTGF-targeting diagnostics and therapeutics for RA.

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Section: Discussionmentioning

confidence: 99%

Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis

et al. 2022

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“…Since aptamers are able to form tertiary conformations with double-stranded regions, Dox can be physically intercalated within the CG-rich, double-stranded region of aptamers to form an aptamer–Dox conjugate [ 109 , 110 ]. Moreover, based on the properties of the CG-rich region, newly designed CG cargo, which contains 10~16 base pair CG repeated sequences, can be used for the linkage with aptamers as drug-intercalating sites to improve the capacity of Dox loading [ 111 ]. Yang et al synthesized a CD33-targeted aptamer–Dox conjugate for CD33-positive AML treatment.…”

Section: Aptamer-mediated Precision Therapy For Hematologic Malignancymentioning

confidence: 99%

The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions

et al. 2022

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Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there are many types of therapeutic drugs (e.g., TKIs, chemotherapy drugs) available for treatment of different malignancies, the relapse, drug resistance and severe side effects due to the lack of selectivity seriously limit their clinical application. Currently, although antibody–drug conjugates have been well established as able to target and deliver highly potent chemotherapy agents into cancer cells for the reduction of damage to healthy cells and have achieved success in leukemia treatment, they still also have shortcomings such as high cost, high immunogenicity and low stability. Aptamers are ssDNA or RNA oligonucleotides that can also precisely deliver therapeutic agents into cancer cells through specifically recognizing the membrane protein on cancer cells, which is similar to the capabilities of monoclonal antibodies. Aptamers exhibit higher binding affinity, lower immunogenicity and higher thermal stability than antibodies. Therefore, in this review we comprehensively describe recent advances in the development of aptamer–drug conjugates (ApDCs) with cytotoxic payload through chemical linkers or direct incorporation, as well as further introduce the latest promising aptamers-based therapeutic strategies such as aptamer–T cell therapy and aptamer–PROTAC, clarifying their bright application, development direction and challenges in the treatment of hematologic malignancies.

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“…Aptamers are widely applied in medical science and molecular biology fields as they have high affinity and specificity to target molecules for diagnostic or therapeutic purposes. Aptamers are emerging tools of biomarkers for clinical diagnostics and therapeutic agents for targeted therapy [ 3 ]. Examples of aptamer-binding targets are bacteria, amino acids, and small metal ions [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Aptamer-Based Biosensors and Cell-Internalizing SELEX Technology for Diagnostic and Therapeutic Application

et al. 2022

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Aptamers are a group of synthetic single-stranded nucleic acids. They are generated from a random library of single-stranded DNA or RNA by a technology named systematic evolution of ligands by exponential enrichment (SELEX). SELEX is a repetitive process to select and identify suitable aptamers that show high affinity and specificity towards target cells. Great strides have been achieved in the design, construction, and use of aptamers up to this point. However, only a small number of aptamer-based applications have achieved widespread commercial and clinical acceptance. Additionally, finding more effective ways to acquire aptamers with high affinity remains a challenge. Therefore, it is crucial to thoroughly examine the existing dearth and advancement in aptamer-related technologies. This review focuses on aptamers that are generated by SELEX to detect pathogenic microorganisms and mammalian cells, as well as in cell-internalizing SELEX for diagnostic and therapeutic purposes. The development of novel aptamer-based biosensors using optical and electrical methods for microbial detection is reported. The applications and limitations of aptamers are also discussed.

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Aptamers: an emerging navigation tool of therapeutic agents for targeted cancer therapy

Abstract: Chemotherapeutic agents have been used for treatment of numerous cancers, but due to poor selectivity and severe systemic side effects, their clinical application is limited. Single-stranded DNA (ssDNA) or RNA...

Cited by 28 publications

References 120 publications

Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis

Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis

The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions

Advances in Aptamer-Based Biosensors and Cell-Internalizing SELEX Technology for Diagnostic and Therapeutic Application

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