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author:

Zhang, Y. (Zhang, Y..) [1] | Zheng, K. (Zheng, K..) [2] | Chen, Z. (Chen, Z..) [3] | Chen, J. (Chen, J..) [4] | Hu, P. (Hu, P..) [5] | Cai, L. (Cai, L..) [6] | Iqbal, Z. (Iqbal, Z..) [7] | Huang, M. (Huang, M..) [8]

Indexed by:

Scopus

Abstract:

Photodynamic antimicrobial chemotherapy (PACT) uses non-traditional mechanisms (free radicals) and is a highly advocated method with promise of inactivating drug-resistance bacteria for local infections. However, there is no related drug used in clinical practice yet. Therefore, new photosensitizers for PACT are under active development. Here, we report the synthesis of a series of photosensitizers with variable positive charges (ZnPc(TAP)4 n+, n = 0, 4, 8, 12) and their inactivation against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The binding kinetics of ZnPc(TAP)4 n+ to bacteria were measured by flow cytometer. Reactive oxygen species (ROS) generation mechanism of the photosensitizers was studied. The toxicity of these compounds to human blood cells was also evaluated. These compounds showed negligible toxicity against human erythocytes but potent bactericidal effects. The compound with 8 positive charges, ZnPc(TAP)4 8+, turned out to have the strongest antibacterial effect among this series of compounds, giving IC50 value of 59 nM at a light dosage of 5 J/cm2 toward E. coli. For a multi-resistant E. coli strain, ZnPc(TAP)4 8+ decreased the bacteria load by 1000-fold at a concentration of 1 μM. Interestingly, ZnPc(TAP)4 12+, instead of ZnPc(TAP)4 8+, exhibited the highest amount of binding to bacteria. Flow cytometry studies showed that all PSs have fast binding onto bacteria, reaching saturated binding within 5 min. Mechanistically, ZnPc(TAP)4 12+ generated ROS primarily via Type I mechanism, while ZnPc(TAP)4 4+ or ZnPc(TAP)4 8+ created ROS by both type I and type II mechanisms. ZnPc(TAP)4 n+ are highly potent, rapid-acting and non-toxic photosensitizers capable of inactivating bacteria. © 2017, Springer-Verlag Berlin Heidelberg.

Keyword:

Mechanistic study; Photodynamic antimicrobial chemotherapy (PACT); Photosensitizer; Phthalocyanine; ROS measurement

Community:

  • [ 1 ] [Zhang, Y.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 2 ] [Zheng, K.]College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042, China
  • [ 3 ] [Chen, Z.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 4 ] [Chen, J.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 5 ] [Hu, P.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 6 ] [Cai, L.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 7 ] [Iqbal, Z.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 8 ] [Iqbal, Z.]Department of Chemistry, COMSATS Institute of Information Technology (CIIT), Abbottabad, KPK 22060, Pakistan
  • [ 9 ] [Huang, M.]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China
  • [ 10 ] [Huang, M.]College of Chemistry, Fuzhou University, Fuzhou, Fujian 350118, China

Reprint 's Address:

  • [Huang, M.]College of Chemistry, Fuzhou UniversityChina

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Source :

Applied Microbiology and Biotechnology

ISSN: 0175-7598

Year: 2017

Issue: 11

Volume: 101

Page: 4691-4700

3 . 3 4

JCR@2017

3 . 9 0 0

JCR@2023

ESI HC Threshold:231

JCR Journal Grade:2

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count: 42

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 0

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