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A Novel Dicationic Boron Dipyrromethene-based Photosensitizer for Antimicrobial Photodynamic Therapy against Methicillin-Resistant Staphylococcus aureus

[ Vol. 28 , Issue. 21 ]

Author(s):

Priyanga Dharmaratne, Ligang Yu, Roy Chi-Hang Wong, Ben Chun-Lap Chan, Kit-Man Lau, Baiyan Wang, Clara Bik San Lau, Kwok-Pui Fung, Dennis Kee-Pui Ng and Margaret Ip*   Pages 4283 - 4294 ( 12 )

Abstract:


Background: We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups.

Methods: The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two mutant strains [AAC(6’)-APH(2”) and RN4220/pUL5054], and ten nonduplicate clinical strains of hospital- and community-associated MRSA. Upon light irradiation, the minimum bactericidal concentrations of compound 3 were in the range of 1.56-50 μM against all the sixteen MRSA strains. Interestingly, compound 3 was not only more active than an analogue in which the ammonium groups are not directly connected to the n-conjugated system (compound 4), but also showed significantly higher (p < 0.05) antibacterial potency than the clinically approved photosensitizer methylene blue. The skin irritation of compound 3 during topical application was tested on human 3-D skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM. In the murine MRSA infected wound study, the colony forming unit reduction of compound 3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log10) compared to other test groups except for the positive control.

Conclusion: In conclusion, the present study provides a scientific basis for future development of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA wound infection.

Keywords:

Methicillin resistant Staphylococcus aureus, antimicrobial photodynamic therapy, boron dipyrromethene, murine wound infection model, photosensitizer, antibacterial potency.

Affiliation:

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T.



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