An AIEgen-Peptide Conjugate as a Phototheranostic Agent for Phagosome-Entrapped Bacteria

被引:109
作者
Qi, Guobin [1 ]
Hu, Fang [1 ]
Kenry [1 ]
Shi, Leilei [1 ]
Wu, Min [1 ]
Liu, Bin [1 ]
机构
[1] Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore
基金
新加坡国家研究基金会;
关键词
aggregation-induced emission; antimicrobial agents; fluorescence imaging; infection; photodynamic therapy; FLUORESCENT-PROBES; CASPASE-1; INFLAMMASOME; RECOGNITION; INFECTION; ENZYME; CELL;
D O I
10.1002/anie.201906099
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The detection and elimination of intracellular bacteria remain a major challenge. In this work, we report an aggregation-induced emission (AIE) bioprobe that can detect bacterial infection and kill bacteria surviving inside macrophages through a dynamic process, notably specific molecular tailoring of the probe by caspase-1 activation in infected macrophages and accumulation of the residue on phagosomes containing bacteria, leading to light-up fluorescent signals. Moreover, the AIEgen can serve as a photosensitizer for generation of reactive oxygen species (ROS); and the average ROS indicator fluorescent signal intensity per unit area in the bacterial phagosomes is approximately 2.7-fold higher than that in the cytoplasm. This, in turn, induces bacteria killing with high efficiency and minimal cytotoxicity towards macrophages. We envision that this specific light-up bioprobe may provide a new approach for selective and sensitive detection and eradication of intracellular bacterial infections.
引用
收藏
页码:16229 / 16235
页数:7
相关论文
共 40 条
[1]   A Dual-Function Antibiotic-Transporter Conjugate Exhibits Superior Activity in Sterilizing MRSA Biofilms and Killing Persister Cells [J].
Antonoplis, Alexandra ;
Zang, Xiaoyu ;
Huttner, Melanie A. ;
Chong, Kelvin K. L. ;
Lee, Yu B. ;
Co, Julia Y. ;
Amieva, Manuel R. ;
Kline, Kimberly A. ;
Wender, Paul A. ;
Cegelski, Lynette .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2018, 140 (47) :16140-16151
[2]   Cell-mediated drug delivery [J].
Batrakova, Elena V. ;
Gendelman, Howard E. ;
Kabanov, Alexander V. .
EXPERT OPINION ON DRUG DELIVERY, 2011, 8 (04) :415-433
[3]   Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of Kanamycin and an Antibacterial Cell-Penetrating Peptide [J].
Brezden, Anna ;
Mohamed, Mohamed F. ;
Nepal, Manish ;
Harwood, John S. ;
Kuriakose, Jerrin ;
Seleem, Mohamed N. ;
Chmielewski, Jean .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 138 (34) :10945-10949
[4]   Chemotaxis-Instructed Intracellular Staphylococcus aureus Infection Detection by a Targeting and Self-Assembly Signal-Enhanced Photoacoustic Probe [J].
Cai, Qian ;
Fei, Yue ;
Hu, Liming ;
Huang, Zhangjian ;
Li, Li-Li ;
Wang, Hao .
NANO LETTERS, 2018, 18 (10) :6229-6236
[5]   Macrophage-Instructed Intracellular Staphylococcus aureus Killing by Targeting Photodynamic Dimers [J].
Cai, Qian ;
Fei, Yue ;
An, Hong-Wei ;
Zhao, Xiao-Xiao ;
Ma, Yang ;
Cong, Yong ;
Hu, Liming ;
Li, Li-Li ;
Wang, Hao .
ACS APPLIED MATERIALS & INTERFACES, 2018, 10 (11) :9197-9202
[6]   Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease [J].
Chen, M ;
Ona, VO ;
Li, MW ;
Ferrante, RJ ;
Fink, KB ;
Zhu, S ;
Bian, J ;
Guo, L ;
Farrell, LA ;
Hersch, SM ;
Hobbs, W ;
Vonsattel, JP ;
Cha, JHJ ;
Friedlander, RM .
NATURE MEDICINE, 2000, 6 (07) :797-+
[7]   Versatile Histochemical Approach to Detection of Hydrogen Peroxide in Cells and Tissues Based on Puromycin Staining [J].
Chung, Clive Yik-Sham ;
Timblin, Greg A. ;
Saijo, Kaoru ;
Chang, Christopher J. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2018, 140 (19) :6109-6121
[8]   Bacterial manipulation of innate immunity to promote infection [J].
Diacovich, Lautaro ;
Gorvel, Jean-Pierre .
NATURE REVIEWS MICROBIOLOGY, 2010, 8 (02) :117-128
[9]   Aggregation-Induced Emission (AIE) Dots: Emerging Theranostic Nanolights [J].
Feng, Guangxue ;
Liu, Bin .
ACCOUNTS OF CHEMICAL RESEARCH, 2018, 51 (06) :1404-1414
[10]   Smart fluorescent probes for imaging macrophage activity [J].
Fernandez, Antonio ;
Vendrell, Marc .
CHEMICAL SOCIETY REVIEWS, 2016, 45 (05) :1182-1196