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Systemic infections caused by life-threatening pathogens represent one of the main factors leading to clinical death. In this study, we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate systemic infections. The nanoplatform is composed of large-pore mesoporous silica nanoparticles (MSNs) grafted by an endoplasmic reticulum-targeting peptide, and a pathogen infection-responsive cap containing the reactive oxygen species-cleavable boronobenzyl acid linker and bovine serum albumin. The capped MSNs exhibited the capacity to high-efficiently load the antimicrobial peptide melittin, and to rapidly release the cargo triggered by H2O2 or the pathogen-macrophage interaction system, but had no obvious toxicity to macrophages. During the interaction with pathogenic Candida albicans cells and macrophages, the melittin-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth, survived macrophages, and suppressed endoplasmic reticulum stress together with pro-inflammatory cytokine secretion. In a systemic infection model, the nanoplatform efficiently prevented kidney dysfunction, alleviated inflammatory symptoms, and protected the mice from death. This study developed a macrophage organelle-targeting nanoplatform for treatment of life-threatening systemic infections.

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Publication history
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Acknowledgements

Publication history

Received: 21 December 2021
Revised: 01 February 2022
Accepted: 04 February 2022
Published: 01 April 2022
Issue date: July 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

We thank Prof. Jeffry Zink for constructive suggestions to this study. This work was supported by the National Natural Science Foundation of China (Nos. 3217010793 and 31870139), Natural Science Foundation of Tianjin (No. 19JCZDJC33800), and Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (No. TSBICIP-KJGG-006).

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