TY - JOUR
T1 - Myeloperoxidase-mimetic nanozyme generates hypochlorous acid for phagosomal bacteria elimination
AU - Chen, Yinglu
AU - Chen, Fangman
AU - He, Xiaoheng
AU - Guo, Chenyang
AU - Cheng, Chuanxu
AU - Wu, Ziping
AU - He, Yan
AU - Zhang, Wensheng
AU - Cui, Feng
AU - Wang, Yingshuai
AU - Yang, Chao
AU - Tang, Jie
AU - Wang, Liang
AU - Shao, Dan
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant No. 32271388), NHMRC Emerging Leadership Investigator Grant (GNT2017974), Natural Science Foundation of Shandong Province (ZR2022QC087) and the National Natural Science Foundation of China (82202317). All animal experiments were conducted in agreement with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals, and the procedures were approved by the Institutional Animal Care and Use Committee of South China University of Technology (Guangzhou, China).
Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant No. 32271388 ), NHMRC Emerging Leadership Investigator Grant ( GNT2017974 ), Natural Science Foundation of Shandong Province ( ZR2022QC087 ) and the National Natural Science Foundation of China ( 82202317 ). All animal experiments were conducted in agreement with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals, and the procedures were approved by the Institutional Animal Care and Use Committee of South China University of Technology (Guangzhou, China).
Publisher Copyright:
© 2024
PY - 2024/2
Y1 - 2024/2
N2 - Fighting against intracellular bacteria that can evade antibiotics is a long-standing challenge. Inspired by the abundant production of hydrogen peroxide (H2O2) within phagosomes during phagocytosis of bacteria, we have devised a myeloperoxidase-like nanozyme capable of facilitating phagosomal reactive oxygen species (ROS) production within the phagosomal environment, while simultaneously enabling the intracellular delivery of antibiotics. These novel nanozymes, denoted as GEN-NPs, has been fabricated through the conjugation of gentamicin (GEN) onto ultrasmall vanadium oxide nanoparticles (NPs). Our results demonstrate that GEN-NPs exhibit superior efficiency in eradicating both intracellular and extracellular bacteria, surpassing free GEN or NPs alone. This enhanced bactericidal activity can be attributed to the bacteria targeting ability and synergistic effect of myeloperoxidase-like GEN-NPs, which catalyze the conversion of abundant H2O2 into bactericide hypochlorous acid (HClO) and ROS within phagosomes. Moreover, the superior therapeutic outcomes of GEN-NPs have been observed across multiple infection models, outperforming the combined effect of GEN and NPs. This study posits that myeloperoxidase-like nanozyme presents a versatile platform for the development of next-generation therapeutics targeting intracellular bacteria.
AB - Fighting against intracellular bacteria that can evade antibiotics is a long-standing challenge. Inspired by the abundant production of hydrogen peroxide (H2O2) within phagosomes during phagocytosis of bacteria, we have devised a myeloperoxidase-like nanozyme capable of facilitating phagosomal reactive oxygen species (ROS) production within the phagosomal environment, while simultaneously enabling the intracellular delivery of antibiotics. These novel nanozymes, denoted as GEN-NPs, has been fabricated through the conjugation of gentamicin (GEN) onto ultrasmall vanadium oxide nanoparticles (NPs). Our results demonstrate that GEN-NPs exhibit superior efficiency in eradicating both intracellular and extracellular bacteria, surpassing free GEN or NPs alone. This enhanced bactericidal activity can be attributed to the bacteria targeting ability and synergistic effect of myeloperoxidase-like GEN-NPs, which catalyze the conversion of abundant H2O2 into bactericide hypochlorous acid (HClO) and ROS within phagosomes. Moreover, the superior therapeutic outcomes of GEN-NPs have been observed across multiple infection models, outperforming the combined effect of GEN and NPs. This study posits that myeloperoxidase-like nanozyme presents a versatile platform for the development of next-generation therapeutics targeting intracellular bacteria.
KW - Hypochlorous acid
KW - Intracellular bacteria
KW - Myeloperoxidase mimetic
KW - Nanozymes
KW - Phagosomes
UR - http://www.scopus.com/inward/record.url?scp=85181915867&partnerID=8YFLogxK
U2 - 10.1016/j.nantod.2023.102137
DO - 10.1016/j.nantod.2023.102137
M3 - Article
AN - SCOPUS:85181915867
SN - 1748-0132
VL - 54
JO - Nano Today
JF - Nano Today
M1 - 102137
ER -