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Doxorubicin-Conjugated Innovative 16-mer DNA Aptamer-Based Annexin A1 Targeted Anti-Cancer Drug Delivery

Title
Doxorubicin-Conjugated Innovative 16-mer DNA Aptamer-Based Annexin A1 Targeted Anti-Cancer Drug Delivery
Author
전병훈
Keywords
annexin A1; DNA1 aptamer; virtual screening; molecular dynamics simulation; binding energy calculations; aptamer-drug conjugate; doxorubicin
Issue Date
2020-09
Publisher
CELL PRESS
Citation
MOLECULAR THERAPY-NUCLEIC ACIDS, v. 21, Page. 1074-1086
Abstract
Aptamers are small, functional single-stranded DNA or RNA oligonucleotides that bind to their targets with high affinity and specificity. Experimentally, aptamers are selected by the systematic evolution of ligands by exponential enrichment (SELEX) method. Here, we have used rational drug designing and bioinformatics methods to design the aptamers, which involves three different steps. First, finding a probable aptamer-binding site, and second, designing the recognition and structural parts of the aptamers by generating a virtual library of sequences, selection of specific sequence via molecular docking, molecular dynamics (MD) simulation, binding energy calculations, and finally evaluating the experimental affinity. Following this strategy, a 16-mer DNA aptamer was designed for Annexin A1 (ANXA1). In a direct binding assay, DNA1 aptamer bound to the ANXA1 with dissociation constants value of 83 nM. Flow cytometry and fluorescence microscopy results also showed that DNA1 aptamer binds specifically to A549, HepG2, U-87 MG cancer cells that overexpress ANXA1 protein, but not to MCF7 and L-02, which are ANXA1 negative cells. We further developed a novel system by conjugating DNA1 aptamer with doxorubicin and its efficacy was studied by cellular uptake and cell viability assay. Also, anti-tumor analysis showed that conjugation of doxorubicin with aptamer significantly enhances targeted therapy against tumors while minimizing overall adverse effects on mice health.
URI
https://www.sciencedirect.com/science/article/pii/S2162253120302274?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/170761
ISSN
2162-2531
DOI
10.1016/j.omtn.2020.07.038
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > EARTH RESOURCES AND ENVIRONMENTAL ENGINEERING(자원환경공학과) > Articles
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