New insights into membrane-camouflaged nanoparticles for the treatment of ETX intoxication

Author:

Xu Jinglin1,Li Dongxue1,Kang Lin2,Liu Tingting2,Huang Jing1,Li Jiaxin2,Lv Jing2,Wang Jing2,Gao Shan2,Li Yanwei2,Yuan Bing2,Zhao Baohua1,Wang Jinglin2,Xin Wenwen2

Affiliation:

1. Hebei Normal University

2. Academy of Military Medical Sciences (AMMS)

Abstract

Abstract Clostridium perfringens ε-toxin (ETX) is the main toxin leading to enterotoxemia of sheep and goats and is classified as a potential biological weapon. In addition, no effective treatment drug is currently available in clinical practice for this toxin. We developed membrane-camouflaged nanoparticles (MNPs) with different membrane origins to neutralize ETX and protect the host from fatal ETX intoxication. We evaluated the safety and therapeutic efficacy of these MNPs in vitro and in vivo. Compared with membranes from karyocytes, such as Madin-Darby canine kidney (MDCK) cells and mouse neuroblastoma N2a cells (N2a cells), membrane from erythrocytes, which do not induce any immune response, are superior in safety. The protective ability of MNPs was evaluated by intravenous injection and lung delivery. We demonstrate that nebulized inhalation is as safe as intravenous injection and that both modalities can effectively protect mice against ETX. In particular, pulmonary delivery of nanoparticles more effectively treated the challenge of inhaled toxins than intravenously injected nanoparticles. Moreover, MNPs can alter the biological distribution of ETX among different organs in the body, and ETX was captured, neutralized and slowly delivered to the liver and spleen, where nanoparticles with ETX could be phagocytized and metabolized. This demonstrates how MNPs treat toxin infections in vivo. Finally, we injected the MNPs into mice in advance to find out whether MNPs can provide preventive protection, and the results showed that the long-cycle MNPs could provide at least a 3-day protection in mice. These findings demonstrate that MNPs provide safe and effective protection against ETX intoxication, provide new insights into membrane choices and delivery routes of nanoparticles, and new evidence of the ability of nanoparticles to provide preventive protection against infections.

Publisher

Research Square Platform LLC

Reference52 articles.

1. Clostridium perfringens epsilon toxin: the third most potent bacterial toxin known;Alves GG;Anaerobe,2014

2. The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin;Rumah KR;PLoS Pathog,2015

3. Clostridium perfringens epsilon toxin induces a rapid change of cell membrane permeability to ions and forms channels in artificial lipid bilayers;Petit L;J Biol Chem,2001

4. Blanch M, Dorca-Arévalo J, Not A, Cases M, Gómez de Aranda I, Martínez-Yélamos A et al. The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression. Molecular and cellular biology. 2018; 38.

5. Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2;Fennessey CM;PLoS ONE,2012

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