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

Aptamer-drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were pr...

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Bibliographic Details
Published in:Pharmaceutics 2022-12, Vol.14 (12), p.2781
Main Authors: Sun, Yang, Geng, Xinyao, Ma, Yue, Qin, Yu, Hu, Shangjiu, Xie, Yuquan, Wang, Ruowen
Format: Article
Language:English
Subjects:
Albumin
albumin complex
Antimitotic agents
Antineoplastic agents
aptamer–drug conjugates
Biotechnology
Cancer therapies
cancer therapy
Chemical properties
Dosage and administration
Drug delivery systems
Drug targeting
Drugs
Ethylenediaminetetraacetic acid
Laboratory animals
Methods
Microscopy
Nanoparticles
Oligonucleotides
targeted delivery
Technology application
Vehicles
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Summary:Aptamer-drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were prepared, Sgc8-paclitaxel by conjugation and Sgc8-gemcitabine, by automated solid-phase synthesis. In vitro experiments showed that F-base-modified ApDCs retain the specificity of the aptamer to target cells and the biological stability is improved. In vivo studies demonstrated that the circulatory time is increased by up to 55 h or longer, as the incorporated F base leads to a stable ApDC-albumin complex as the formulation for targeted delivery. Moreover, conjugated drug molecules were released efficiently and the drug (paclitaxel) concentration in the tumor site was improved. The results demonstrate that an F-base-directed ApDC-albumin complex is a potential platform for drug delivery and targeted cancer therapy.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14122781