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用于靶向……的反义抗菌剂的树枝状多肽递送系统的优化

Optimization of Dendritic Polypeptide Delivery System for Antisense Antibacterial Agents Targeting .

作者信息

Li Yaoyao, Hu Yue, Kamal Zul, Chen Yamiao, Xue Xiaoyan, Yao Shuting, Zhao Hui, Jia Min, Li Yuan, Wang Zheng, Li Mingkai, Chen Zhou

机构信息

College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an 712046, China.

Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China.

出版信息

ACS Omega. 2024 Apr 30;9(19):20966-20975. doi: 10.1021/acsomega.4c00114. eCollection 2024 May 14.

DOI:10.1021/acsomega.4c00114
PMID:38764644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11097154/
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 .

摘要

对于耐药性（）感染，迫切需要一种新的治疗策略。反义抗菌剂是很有前景的抗菌剂，高效的药物递送系统对于反义抗菌剂的进一步开发是必要的。为了开发新的反义药物并进一步提高递送效率和安全性，我们设计并筛选了新的反义序列，并优化了先前研究中发现的树枝状多肽纳米颗粒（DP-AD）。将N/P比从8:1优化到6:1，并全面研究了优化后的DP-AD的正电荷数。结果表明，N/P比和正电荷数对DP-AD的粒径分布和转运效率没有显著影响。降低N/P比可显著降低DP-AD的细胞毒性，但不影响其递送效率和抗菌活性。然而，在耐药菌株中，带有10个正电荷的DP-AD7的抗菌活性高于带有8个正电荷的DP-AD8。我们的研究发现了一种靶向的新型反义寡核苷酸，并得出结论，带有10个正电荷的DP-AD7是现阶段的最佳选择，这为治疗耐药性（）提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/18f63d1737b4/ao4c00114_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/c68471722141/ao4c00114_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/ed0710b5a77b/ao4c00114_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/4e629c201841/ao4c00114_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/6539776259a3/ao4c00114_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/fba095b3e914/ao4c00114_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/397cbc86263f/ao4c00114_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/18f63d1737b4/ao4c00114_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/c68471722141/ao4c00114_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/ed0710b5a77b/ao4c00114_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/4e629c201841/ao4c00114_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/6539776259a3/ao4c00114_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/fba095b3e914/ao4c00114_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/397cbc86263f/ao4c00114_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82b/11097154/18f63d1737b4/ao4c00114_0007.jpg

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本文引用的文献

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