Spring viremia of carp virus (SVCV), as a high pathogenicity pathogen, has seriously restricts the healthy and sustainable development of cyprinid farming industry. In this study, we selected 5-Fluorouracil (5-Fu) as the drug model based on zeolitic imidazolate framework-8 (ZIF-8) to construct a drug delivery system (5-Fu@ZIF-8), and the anti-SVCV activity was detected in vitro and in vivo . The results showed 5-Fu@ZIF-8 was uniform cubic particle with truncated angle and smooth surface, and the particle size was 90 nm. The anti-SVCV activity in vitro results showed that the highest inhibition rate of 5-Fu was 77.93% at 40 mg/L and the inhibitory concentration at half-maximal activity (IC 50 ) was 20.86 mg/L. For 5-Fu@ZIF-8, the highest inhibition rate was 91.36% at 16 mg/L, and the IC 50 value was 5.85 mg/L. In addition, the cell viability was increased by 18.1% after 5-Fu treatment. Similarly, after 5-Fu@ZIF-8 treatment, the cell viability increased by 27.3%. Correspondingly, in vivo experimental results showed the viral loads reduced by 18.1% on the days 7 and the survival rate increased to 19.4% at 80 mg/L after 5-Fu treatment. For 5-Fu@ZIF-8, the viral loads reduced by 41.2% and the survival rate increased to 54.8%. Mechanistically, 5-Fu inhibits viral replication by regulating p53 expression and promoting early apoptosis in infected cells. All results indicated that 5-Fu@ZIF-8 improved the anti-SVCV activity; it may be a potential strategy to construct a drug-loaded system with ZIF-8 as a carrier for the prevention and treatment of aquatic diseases.
Xinfang Li,Qinan Xu,Jing Wang,Peng Zhang,Youxiang Wang,Jian Ji
A coated microneedle patch is a reliable way to load gene on a surface as a transdermal gene delivery platform. But there are many limitations to the traditional methods to fabricate a coated microneedle patch, such as the fact that they are time consuming or the difficulty in controlling the loading content. In this research, ultrasonic spraying technology, as an industrialized production method, was first used to fabricate a gene-coated microneedle patch. First, the p53 expression plasmid (p53 DNA) was ultrasonically sprayed on a polycaprolactone (PCL) microneedle patch (D@MNP). To promote the transfection efficiency, polycation polyethylenimine (PEI), as a vector, was then ultrasonically sprayed on D@MNP (P@D@MNP). From the experimental results, although two layers were sprayed step by step, no obvious stratification could be observed. The vector PEI interweaved with genes and inhibited the gene release profile, but it changed the released naked genes to positively charged complexes, which would promote gene transfection efficiency. In subsequent in vivo experiments, the anti-tumor efficacy of the “P@D@MNP treated group” could reach 84.7%, although it had the lowest gene release profile. In contrast, the anti-tumor efficacy of the “intravenous injection group” and “D@MNP treated group” was only 24.3% and 59.3%, respectively. Overall, P@D@MNP was a safe and efficient device to treat the subdermal tumor. Ultrasonic spraying technology provided an industrialized method to fabricate the coated microneedle patch as a transdermal gene/drug delivery platform.
危险品化学品经营许可证（带存储）