Issue 41, 2022

An inflammation-targeted nanoparticle with bacteria forced release of polymyxin B for pneumonia therapy

Abstract

The epidemic of multidrug-resistant Gram-negative bacteria is an ever-growing global concern. Polymyxin B (PMB), a kind of “old fashioned” antibiotic, has been revived in clinical practice and mainly used as last-line antibiotics for otherwise untreatable serious infections because the incidence of the resistance to PMB is currently relatively low in comparison with other antibiotics in vivo owing to the unique bactericidal mechanism of PMB. However, serious adverse side effects, including nephrotoxicity and neurotoxicity, hamper its clinical application. Herein, we describe the development of a nanoparticle that can target sites of inflammation and forcedly release PMB specifically in the area of Gram-negative bacteria. This particle was constructed through the electrostatic self-assembly of hyaluronic acid (HA) and PMB molecules in order to realize the safe and effective treatment of pneumonia. After systemic administration, PMB-HA nanoparticles were found to actively accumulate in the lungs, precisely target the CD44 receptors over-expressed on the membrane of activated endothelial cells in inflammatory sites, and then come into contact with the bacteria resident in the damaged alveolar-capillary membrane. Due to the electrostatic and hydrophobic interactions between PMB and the lipopolysaccharide (LPS) in the outer membranes of bacteria, the PMB molecules in the PMB-HA nanoparticles are expected to escape from the nanoparticles to insert into the bacteria via competitive binding with LPS. Through shielding the cationic nature of PMB, PMB-HA nanoparticles also possess outstanding biosafety performance in comparison to free PMB. It is thus believed that this smart delivery system may pave a new way for the resurrection of PMB in the future clinical treatment of bacterial inflammatory diseases.

Graphical abstract: An inflammation-targeted nanoparticle with bacteria forced release of polymyxin B for pneumonia therapy

Supplementary files

Article information

Article type
Paper
Submitted
12 Apr. 2022
Accepted
01 Aug. 2022
First published
03 Aug. 2022

Nanoscale, 2022,14, 15291-15304

An inflammation-targeted nanoparticle with bacteria forced release of polymyxin B for pneumonia therapy

P. Zhang, Q. Ouyang, T. Zhai, J. Sun, J. Wu, F. Qin, N. Zhang, S. Yue, X. Yang, H. Zhang, Y. Hou, L. Deng, F. Wang, Q. Zhan, Q. Yu, M. Qin and Z. Gan, Nanoscale, 2022, 14, 15291 DOI: 10.1039/D2NR02026B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements