Khalil Abnous1,2, Noor Mohammad Danesh3, Mohammad Ramezani1, Fahimeh Charbgoo1, Amirhossein Bahreyni1, Seyed Mohammad Taghdisi4,5. 1. a Pharmaceutical Research Center, Pharmaceutical Technology Institute , Mashhad University of Medical Sciences , Mashhad , Iran. 2. b Department of Medicinal Chemistry, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran. 3. c Research Institute of Sciences and New Technology , Mashhad , Iran. 4. d Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute , Mashhad University of Medical Sciences , Mashhad , Iran. 5. e Department of Pharmaceutical Biotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
Abstract
OBJECTIVES: Here, a novel cruciform DNA nanostructure was developed for targeted delivery of doxorubicin (Dox), as an anticancer agent, to lung (A549 cells) and breast (4T1 cells) cancer cells. The cruciform DNA nanostructure consisted of AS1411 aptamer as targeting agent and Forkhead Box Protein M1(FOXM1) aptamer as therapeutic agent. METHODS: MTT assay, fluorescence imaging, flow cytometry analysis, and in vivoantitumor efficacy were performed to evaluate the function of the Dox-DNA nanostructure complex. RESULTS: The presented delivery system benefited from tumor targeting, high stability in serum and simple construction. The Dox-DNA nanostructure complex showed a noticeable higher internalization degree into A549 and 4T1 cells (target), overexpressing nucleolin on their cell membranes, compared to CHO cells (nontarget, nucleolin negative). Moreover, the results of MTT assay exhibited that Dox-DNA nanostructure complex significantly decreased cell viability in A549 and 4T1 cells compared to CHO cells, which significantly preserved their viability. Besides, Dox-DNA nanostructure complex significantly reduced tumor growth in tumor-bearing mice in comparison with Dox and DNA nanostructure treatments. CONCLUSION: These findings confirmed that synergistic combination of FOXM1 aptamer and Dox into Dox-DNA nanostructure complex enhanced antitumor effectiveness and reduced toxicity toward nontarget cells, opening up new insights in cancer treatment.
OBJECTIVES: Here, a novel cruciform DNA nanostructure was developed for targeted delivery of doxorubicin (Dox), as an anticancer agent, to lung (A549 cells) and breast (4T1 cells) cancer cells. The cruciform DNA nanostructure consisted of AS1411 aptamer as targeting agent and Forkhead Box Protein M1(FOXM1) aptamer as therapeutic agent. METHODS:MTT assay, fluorescence imaging, flow cytometry analysis, and in vivoantitumor efficacy were performed to evaluate the function of the Dox-DNA nanostructure complex. RESULTS: The presented delivery system benefited from tumor targeting, high stability in serum and simple construction. The Dox-DNA nanostructure complex showed a noticeable higher internalization degree into A549 and 4T1 cells (target), overexpressing nucleolin on their cell membranes, compared to CHO cells (nontarget, nucleolin negative). Moreover, the results of MTT assay exhibited that Dox-DNA nanostructure complex significantly decreased cell viability in A549 and 4T1 cells compared to CHO cells, which significantly preserved their viability. Besides, Dox-DNA nanostructure complex significantly reduced tumor growth in tumor-bearing mice in comparison with Dox and DNA nanostructure treatments. CONCLUSION: These findings confirmed that synergistic combination of FOXM1 aptamer and Dox into Dox-DNA nanostructure complex enhanced antitumor effectiveness and reduced toxicity toward nontarget cells, opening up new insights in cancer treatment.
Entities:
Keywords:
AS1411; Cruciform DNA nanostructure; FOXM1 aptamer; cancer treatment; doxorubicin
Authors: Luana di Leandro; Francesco Giansanti; Sabrina Mei; Sara Ponziani; Martina Colasante; Matteo Ardini; Francesco Angelucci; Giuseppina Pitari; Michele d'Angelo; Annamaria Cimini; Maria Serena Fabbrini; Rodolfo Ippoliti Journal: Front Pharmacol Date: 2021-04-15 Impact factor: 5.810
Authors: Frank H T Nelissen; Wenny J M Peeters; Timo P Roelofs; Anika Nagelkerke; Paul N Span; Hans A Heus Journal: Pharmaceuticals (Basel) Date: 2021-04-09