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Intranasal administration of a multiplex targeting SCLMs@FEN1-hpDNAs with synergistic baicalein for pulmonary anti-viral treatment

ABSTRACT: Here we reported an anti-viral strategy for SARS-CoV-2 infection: intranasal administration of silica cross-linked micelles (SCLMs) encapsulating in vitro purified NES-FEN1-NES protein and a set of hpDNAs (shorted as SCLMs@FEN1-hpDNAs). The set of hpDNAs multiplex targeted SARS-CoV-2’s N gene RNA and the host Ctsl gene mRNA. In vitro experiments demonstrated the purified NES-FEN1-NES protein transfected into cells has efficient mRNA knockdown ability when guided by hpDNAs. The intranasal administration of SCLMs exhibited high pulmonary accessibility, and SCLMs@FEN1-hpDNAs effectively downregulated targeted gene expression in vivo. The efficacy is enhanced by synergistic intranasal baicalein by improving cellular uptake and anti-inflammatory effects. In a mouse model of SARS-CoV-2 infection, the combination with baicalein and SCLMs@FEN1-hpDNAs inhibited the virus replication, improved survival rates, and reduced neuroinflammation. This study highlights the potential of intranasal SCLMs@FEN1-hpDNAs with baicalein as a promising approach for treating respiratory diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE284624 | GEO | 2024/12/19

REPOSITORIES: GEO

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Project description:Baicalein, a purified flavonoid compound with defined chemical structure extracted from the dry roots of Scutellaria radix that is a broadly used herb in China, has been proved to possess significant anti-hepatoma activity by inhibiting cell proliferation, invasion, metastasis and inducing apoptosis, autophagy via several cancer-related signaling molecules. In recent years, emerging studies have demonstrated that Chinese medicinal herbs can exert their anti-tumor effects through targeting lncRNAs，such as curcumin, camptothecin, resveratrol，paclitaxel. However, there is still no related report about the effects of baicalein on lncRNA expression profile when it exerts its inhibition on hepatoma tumor growth. To investigate whether the antitumor effect of baicalein is related to its modulation of lncRNA expression in hepatocellular carcinoma (HCC), we profiled the lncRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using lncRNA microarray and detected the changes by comparing the lncRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of lncRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations. To investigate whether the antitumor effect of baicalein is related to its modulation of lncRNA expression in hepatocellular carcinoma (HCC), we profiled the miRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using miRNA microarray and detected the changes by comparing the lncRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of lncRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations.

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Intranasal administration of a multiplex targeting SCLMs@FEN1-hpDNAs with synergistic baicalein for pulmonary anti-viral treatment

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