Artificial Base-Directed In Vivo Formulation of Aptamer–Drug Conjugates with Albumin for Long Circulation and Targeted Delivery

Sun, Yang; Geng, Xinyao; Ma, Yue; Qin, Yu; Hu, Shangjiu; Xie, Yuquan; Wang, Ruowen

doi:10.3390/pharmaceutics14122781

Cited by 5 publications

(2 citation statements)

References 29 publications

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“…The linker connects the aptamer with the drug molecule, which exerts a therapeutic effect. The aptamer serves as a recognition ligand, guiding the therapeutic drug to a disease site or regulating the biological function of targeted biomarkers [335]. Nucleic acid aptamers are oligonucleotide sequences identified using live cell-based index enriched ligand system evolution technology (Cell SELEX) that can bind to various targets with high affinity and specificity [336].…”

Section: Aptamer-drug Conjugates (Apdcs)mentioning

confidence: 99%

Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice

Zhou,

Lu,

Liu

et al. 2024

Exp Hematol Oncol

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A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity of antibodies with the cytotoxicity of chemotherapeutic drugs to reduce adverse reactions by preferentially targeting the payload to the tumor. The structure of ADCs has also provided inspiration for the development of additional drug conjugates. In recent years, drug conjugates such as ADCs, peptide‒drug conjugates (PDCs) and radionuclide drug conjugates (RDCs) have been approved by the Food and Drug Administration (FDA). The scope and application of drug conjugates have been expanding, including combination therapy and precise drug delivery, and a variety of new conjugation technology concepts have emerged. Additionally, new conjugation technology-based drugs have been developed in industry. In addition to chemotherapy, targeted therapy and immunotherapy, drug conjugate therapy has undergone continuous development and made significant progress in treating lung cancer in recent years, offering a promising strategy for the treatment of this disease. In this review, we discuss recent advances in the use of drug conjugates for lung cancer treatment, including structure-based drug design, mechanisms of action, clinical trials, and side effects. Furthermore, challenges, potential approaches and future prospects are presented.

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Section: Aptamer-drug Conjugates (Apdcs)mentioning

confidence: 99%

Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice

Zhou,

Lu,

Liu

et al. 2024

Exp Hematol Oncol

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“… 12 Similarly, hydrophobic F bases improved nuclease resistance ability, and aptamers coupled with F and paclitaxel (Sgc8-F-PTX) had significantly higher stability than Sgc8, perhaps because F bases could bind with albumin to form a stable complex. 13 , 14 …”

Section: Characteristics Of Aptamersmentioning

confidence: 99%

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology

Cao¹,

Zhang²,

Xiong³

2023

IJN

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Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-β receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.

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Functionalizing Sgc8‐Paclitaxel Conjugates with F‐Base Modifications: Targeted Drug Delivery with Optimized Cardiac Safety

Ma,

Liao,

et al. 2024

ChemMedChem

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Recent advancements in cancer treatment have improved patient prognoses, but chemotherapy‐induced cardiotoxicity remains a prevalent concern. This study explores the potential of F‐base‐modified aptamers for targeted drug delivery, focusing on their impact on cardiotoxicity. From the phosphoramidite, F‐base functionalized Sgc8‐F23 was prepared in an automated and programmable way, which was further reacted with Paclitaxel (PTX) to give the F‐base modified aptamer Sgc8‐paclitaxel conjugates (Sgc8‐F23‐PTX) efficiently. The conjugate exhibits prolonged circulation time and enhanced efficacy as precision anticancer drug delivery system. Echocardiographic assessments reveal no exacerbation of cardiac dysfunction post‐Acute Myocardial Infarction (AMI), and no pathological changes or increased apoptosis in non‐infarcted cardiac regions. Autophagy pathway analysis shows no discernible differences in Sgc8‐F23‐PTX‐treated cardiomyocytes compared to controls, contrasting with increased autophagy with Nanoparticle albumin‐bound ‐Paclitaxel (Nab‐PTX). Similarly, apoptosis analysis shows no significant distinctions. Moreover, Sgc8‐F23‐PTX exhibits no inhibitory effects on hERG, hNav1.5, or hCav1.2 channels. These findings suggest the safety and efficacy of F‐base‐modified Sgc8 aptamers for targeted drug delivery, holding potential clinical applications. Further research is warranted for clinical translation and exploration of other drug carriers.

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Artificial Base-Directed In Vivo Formulation of Aptamer–Drug Conjugates with Albumin for Long Circulation and Targeted Delivery

Cited by 5 publications

References 29 publications

Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice

Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology

Functionalizing Sgc8‐Paclitaxel Conjugates with F‐Base Modifications: Targeted Drug Delivery with Optimized Cardiac Safety

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