AI Article Synopsis
- * The study developed and optimized dendritic polypeptide nanoparticles (DP-AD) for better efficiency and safety in delivering antisense drugs, finding that a lower N/P ratio reduces toxicity without compromising effectiveness.
- * The optimal formulation identified was DP-AD7 with 10 positive charges, which demonstrated greater antibacterial activity against drug-resistant strains compared to alternatives, thus offering a potential new strategy for treatment.
Article Abstract
There is an urgent requirement for a novel treatment strategy for drug-resistant () infection. Antisense antimicrobials are promising antimicrobials, and efficient drug delivery systems are necessary for the further development of antisense antimicrobials. To develop new antisense drugs and further improve delivery efficiency and safety, we designed and screened new antisense sequences and optimized dendritic polypeptide nanoparticles (DP-AD) discovered in previous studies. The N/P ratio is optimized from 8:1 to 6:1, and the positive charge number of the optimized DP-AD is studied comprehensively. The results show that the N/P ratio and positive charge number have no significant effect on the particle size distribution and transport efficiency of DP-AD. Reducing the N/P ratio can significantly reduce the cytotoxicity of DP-AD, but it does not affect its delivery efficiency and antibacterial activity. However, in drug-resistant strains, the antibacterial activity of DP-AD7 with 10 positive charges is higher than that of DP-AD8 with 8 positive charges. Our research discovered a novel ASOs targeting and concluded that DP-AD7 with 10 positive charges was the optimal choice at the current stage, which provided a promising strategy for the treatment of drug-resistant .
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097154 | PMC |
| http://dx.doi.org/10.1021/acsomega.4c00114 | DOI Listing |
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