PMID- 36905740 OWN - NLM STAT- MEDLINE DCOM- 20230418 LR - 20230418 IS - 1873-3557 (Electronic) IS - 1386-1425 (Linking) VI - 295 DP - 2023 Jul 5 TI - Spectroscopic, calorimetric and cytotoxicity studies on the combined binding of daunorubicin and acridine orange to a DNA tetrahedron. PG - 122583 LID - S1386-1425(23)00268-8 [pii] LID - 10.1016/j.saa.2023.122583 [doi] AB - Chemotherapy-phototherapy (CTPT) combination drugs co-loaded by targeted DNA nanostructures can achieve controlled drug delivery, reduce toxic side effects and overcome multidrug resistance. Herein, we constructed and characterized a DNA tetrahedral nanostructure (MUC1-TD) linked with the targeting aptamer MUC1. The interaction of daunorubicin (DAU)/acridine orange (AO) alone and in combination with MUC1-TD and the influence of the interaction on the cytotoxicity of the drugs were evaluated. Potassium ferrocyanide quenching analysis and DNA melting temperature assays were used to demonstrate the intercalative binding of DAU/AO to MUC1-TD. The interactions of DAU and/or AO with MUC1-TD were analyzed by fluorescence spectroscopy and differential scanning calorimetry. The number of binding sites, binding constant, entropy and enthalpy changes of the binding process were obtained. The binding strength and binding sites of DAU were higher than those of AO. The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. In vitro cytotoxicity studies demonstrated that the loading of MUC1-TD augmented the inhibitory effects of DAU and AO and the synergistic cytotoxic effects of DAU + AO on MCF-7 cells and MCF-7/ADR cells. Cell uptake studies showed that the loading of MUC1-TD was beneficial in promoting the apoptosis of MCF-7/ADR cells due to its enhanced targeting to the nucleus. This study has important guiding significance for the combined application of DAU and AO co-loaded by DNA nanostructures to overcome multidrug resistance. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Zhang, Xinpeng AU - Zhang X AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: z954004605@163.com. FAU - Li, Xinyu AU - Li X AD - School of Chemistry and Chemical Engineering, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: Lixinyu3564@163.com. FAU - Wang, Danfeng AU - Wang D AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: 17865814851@163.com. FAU - Weng, Tianxin AU - Weng T AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: tianxinweng2020@126.com. FAU - Wang, Lu AU - Wang L AD - School of Chemistry and Chemical Engineering, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: 17863526817@163.com. FAU - Yuan, Lixia AU - Yuan L AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: Yuan1072165059@163.com. FAU - Wang, Qingpeng AU - Wang Q AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: lywqp@126.com. FAU - Liu, Jie AU - Liu J AD - School of Chemistry and Chemical Engineering, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: liujielcu@126.com. FAU - Wu, Yushu AU - Wu Y AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: yushuwu@126.com. FAU - Liu, Min AU - Liu M AD - Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng 252059, China; School of Chemistry and Chemical Engineering, Liaocheng University, Hunan Road, Liaocheng 252059, China. Electronic address: panpanliumin@163.com. LA - eng PT - Journal Article DEP - 20230306 PL - England TA - Spectrochim Acta A Mol Biomol Spectrosc JT - Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy JID - 9602533 RN - ZS7284E0ZP (Daunorubicin) RN - F30N4O6XVV (Acridine Orange) RN - 0 (Antineoplastic Agents) RN - 9007-49-2 (DNA) SB - IM MH - *Daunorubicin/pharmacology/chemistry MH - Acridine Orange MH - *Antineoplastic Agents/pharmacology MH - Drug Delivery Systems MH - DNA/genetics OTO - NOTNLM OT - Binding affinity OT - Calorimetry OT - Combined drugs OT - Cytotoxicity OT - DNA nanostructures OT - Spectroscopy COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/12 06:00 MHDA- 2023/04/18 10:16 CRDT- 2023/03/11 18:06 PHST- 2022/12/06 00:00 [received] PHST- 2023/02/23 00:00 [revised] PHST- 2023/03/01 00:00 [accepted] PHST- 2023/04/18 10:16 [medline] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/11 18:06 [entrez] AID - S1386-1425(23)00268-8 [pii] AID - 10.1016/j.saa.2023.122583 [doi] PST - ppublish SO - Spectrochim Acta A Mol Biomol Spectrosc. 2023 Jul 5;295:122583. doi: 10.1016/j.saa.2023.122583. Epub 2023 Mar 6.