PMID- 38404643
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240227
IS  - 2452-199X (Electronic)
IS  - 2452-199X (Linking)
VI  - 35
DP  - 2024 May
TI  - High-performance lung-targeted bio-responsive platform for severe 
      colistin-resistant bacterial pneumonia therapy.
PG  - 517-533
LID - 10.1016/j.bioactmat.2024.02.017 [doi]
AB  - Polymyxins are the last line of defense against multidrug-resistant (MDR) 
      Gram-negative bacterial infections. However, this last resort has been threatened 
      by the emergence of superbugs carrying the mobile colistin resistance gene-1 
      (mcr-1). Given the high concentration of matrix metalloproteinase 3 (MMP-3) in 
      bacterial pneumonia, limited plasma accumulation of colistin (CST) in the lung, 
      and potential toxicity of ionic silver (Ag(+)), we designed a feasible clinical 
      transformation platform, an MMP-3 high-performance lung-targeted bio-responsive 
      delivery system, which we named "CST&Ag@CNMS". This system exhibited excellent 
      lung-targeting ability (>80% in lungs), MMP-3 bio-responsive release property 
      (95% release on demand), and synergistic bactericidal activity in vitro (2-4-fold 
      minimum inhibitory concentration reduction). In the mcr-1(+) CST-resistant murine 
      pneumonia model, treatment with CST&Ag@CNMS improved survival rates (70% vs. 
      20%), reduced bacteria burden (2-3 log colony-forming unit [CFU]/g tissue), and 
      considerably mitigated inflammatory response. In this study, CST&Ag@CNMS 
      performed better than the combination of free CST and AgNO(3). We also 
      demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in 
      vitro and in vivo. These findings indicate the clinical translational potential 
      of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant 
      bacteria carrying mcr-1.
CI  - (c) 2024 The Authors.
FAU - Cheng, Decui
AU  - Cheng D
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
AD  - Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment 
      of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, 
      Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 
      200025, China.
FAU - Tian, Rui
AU  - Tian R
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
AD  - Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment 
      of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, 
      Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 
      200025, China.
FAU - Pan, Tingting
AU  - Pan T
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
FAU - Yu, Qiang
AU  - Yu Q
AD  - Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment 
      of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, 
      Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 
      200025, China.
FAU - Wei, Li
AU  - Wei L
AD  - Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment 
      of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, 
      Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 
      200025, China.
FAU - Liyin, Jiaozhi
AU  - Liyin J
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
FAU - Dai, Yunqi
AU  - Dai Y
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
FAU - Wang, Xiaoli
AU  - Wang X
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
FAU - Tan, Ruoming
AU  - Tan R
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
FAU - Qu, Hongping
AU  - Qu H
AD  - Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
FAU - Lu, Min
AU  - Lu M
AD  - Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment 
      of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, 
      Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 
      200025, China.
LA  - eng
PT  - Journal Article
DEP - 20240221
PL  - China
TA  - Bioact Mater
JT  - Bioactive materials
JID - 101685294
PMC - PMC10885821
OTO - NOTNLM
OT  - Bacterial severe pneumonia
OT  - Colistin-resistant bacteria
OT  - Lung targeting
OT  - MCR-1
OT  - Matrix metalloproteinase 3
OT  - Synergistic action
COIS- None.
EDAT- 2024/02/26 06:44
MHDA- 2024/02/26 06:45
PMCR- 2024/02/21
CRDT- 2024/02/26 04:30
PHST- 2023/10/23 00:00 [received]
PHST- 2024/02/12 00:00 [revised]
PHST- 2024/02/14 00:00 [accepted]
PHST- 2024/02/26 06:45 [medline]
PHST- 2024/02/26 06:44 [pubmed]
PHST- 2024/02/26 04:30 [entrez]
PHST- 2024/02/21 00:00 [pmc-release]
AID - S2452-199X(24)00062-8 [pii]
AID - 10.1016/j.bioactmat.2024.02.017 [doi]
PST - epublish
SO  - Bioact Mater. 2024 Feb 21;35:517-533. doi: 10.1016/j.bioactmat.2024.02.017. 
      eCollection 2024 May.