Improving the Transduction Efficiency and Antitumor Effect of Conditionally Replicative Adenovirus by Application of 6-cyclohexyl Methyl-β-D-maltoside

Wenjing Lu; Yaping Fang; Xue Meng; Xiaoli Wang; Wenbo Liu; Mengdong Liu; Ping Zhang

doi:10.3390/molecules28020528

Molecules (Jan 2023)

Improving the Transduction Efficiency and Antitumor Effect of Conditionally Replicative Adenovirus by Application of 6-cyclohexyl Methyl-β-D-maltoside

Wenjing Lu,
Yaping Fang,
Xue Meng,
Xiaoli Wang,
Wenbo Liu,
Mengdong Liu,
Ping Zhang

Affiliations

Wenjing Lu: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
Yaping Fang: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
Xue Meng: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
Xiaoli Wang: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
Wenbo Liu: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
Mengdong Liu: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China
Ping Zhang: Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China

DOI: https://doi.org/10.3390/molecules28020528
Journal volume & issue: Vol. 28, no. 2
p. 528

Abstract

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As a tumor-targeting oncolytic adenovirus (Ad), conditionally replicating adenovirus (CRAd) can access the cell interior by binding to coxsackievirus-Ad receptors (CARs) and specifically replicate and destroy cancer cells without lethal effects on normal cells. The transduction efficiency of CRAd is highly dependent on the number of CARs on the cell membrane. However, not all tumor cells highly express CARs; therefore, improving the transduction efficiency of CRAd is beneficial for improving its antitumor effect. In this study, 6-cyclohexyl methyl-β-D-maltoside (6-β-D), as maltoside transfection agent, showed several advantages, including high transfection efficiency, low toxicity, and potential for intensive use and easy operation. With pretreatment of cancer cells with low concentration of 6-β-D (≤5 μg/mL), the transduction efficiency of “model” Ad (eGFP-Ad) was improved 18-fold compared to eGFP-Ad alone. 6-β-D improved the antitumor effect of CRAd while being safe for normal cells, in which treatment with 6-β-D helped the lethal effects of CRAd at a multiplicity-of-infection ratio of 10 (MOI 10) achieve the oncolytic outcomes of MOI 50. This means that if CRAd is combined with 6-β-D, the amount of CRAd used in clinical practice could be greatly reduced without diminishing its curative effect or exposing patients to the potential side effects of high-titer CRAd. Finally, the underlying mechanism of antitumor effect of CRAd + 6-β-D was primarily investigated, and we found that 6-β-D increased the virus’s replication in cancer cells at the early stage of infection and activated the apoptosis signaling pathway at the late stage of the cell cycle. This research will provide an effective technical reference for further improving Ad-mediated cancer gene therapy in clinical practice.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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