Molecular study of AS1411 aptamer binding for application of anti-cancer drug carrier

การศึกษาการยึดจับของแอพทาเมอร์ชนิด AS1411 ด้วยการคำนวณเชิงโมเลกุลเพื่อการประยุกต์ใช้งานเป็นสารนำส่งยาต้านมะเร็ง

Name: Paphada Watcharapo

keyword: Molecular dynamics simulation

; AS1411 aptamer

; Nucleolin

; Doxorubicin

; Drug delivery system

Abstract: Cancer is the leading cause of death, which has a significant effect on public healthcare management. Most patients have suffered from side effects of therapeutic drugs, partly because of a lack of specificity. To improve drug specificity, the incorporation of recognition ligands is a fascinating strategy that could minimize side effects. Aptamers, single-stranded oligonucleotides, are promising candidates for incorporation with chemotherapeutic agents because they exhibit the specific binding ability to their targets. This work investigated the possibility of using a modified AS1411 aptamer as a carrier of doxorubicin (Dox), an anticancer drug, to the cancer cell. We have used molecular dynamics (MD) simulation to study the interaction between nucleolin and aptamer in either the absence or presence of Dox. In addition, we prepared doxorubicin-loaded aptamer train (Dox-AT) to experimentally confirm the specific recognition of nucleolin on SW480 cells and effectively deliver the therapeutic drug to the target cells. MD simulation results provided information on fluctuations, conformational changes, binding energy, and their binding sites. The results showed that the fluctuation of amino acid residues in nucleolin was decreased due to the binding interaction with AS22nt and Dox-AS22nt. Binding energy revealed that Dox had no role in the nucleolin-aptamer interaction. This suggests the role of AS22nt aptamer as a Dox carrier towards nucleolin. For the experimental parts, the successful preparation of AT complex was characterized by gel electrophoresis and dynamic light scattering. Dox was loaded into the AT complex, which was verified by fluorescence spectrophotometry. The AT was able to be internalized into SW480 cells, as verified by fluorescence microscopy. The cytotoxicity result indicated that AT inhibited the proliferation of SW480. The success of this work demonstrated that molecular dynamics simulation could fill in more understanding of the interaction between AS1411 aptamer, Dox, and nucleolin and the developed aptamer-based drug carrier is a promising system for anticancer drug delivery that could be beneficial to cancer-suffering patients

Thammasat University. Thammasat University Library

Address: BANGKOK

Email: preserv@tu.ac.th

Name: Boonchoy Soontornworajit

Role: advisor

Name: Yuthana Tantirungrotechai

Role: co-advisor

Created: 2022

Modified: 2023-12-01

Issued: 2023-12-01

วิทยานิพนธ์/Thesis

application/pdf

DOI: 10.14457/TU.the.2022.577

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Chemistry

Grantor: Thammasat University

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