Research Article

Antimicrobial photodynamic therapy with decacationic monoadducts and bisadducts of [70]fullerene: in vitro and in vivo studies

Department of Infectious Diseases, First Affiliated College & Hospital, Guangxi Medical University, Nanning, 530021, China

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

Department of Dermatology, Harvard Medical School, Boston,MA 02115, USA

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Min Wang

Department of Chemistry, University of Massachusetts, Lowell,MA 01854, USA

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Tianhong Dai

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

Department of Dermatology, Harvard Medical School, Boston,MA 02115, USA

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Felipe F Sperandio

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

Department of Oral Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, SP 05508-000, Brazil

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Ying-Ying Huang

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

Department of Dermatology, Harvard Medical School, Boston,MA 02115, USA

Aesthetic & Plastic Center of Guangxi Medical University, Nanning, China

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Yi Xuan

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA

Tufts University, Medford,MA 02155, USA

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Long Y Chiang

Department of Chemistry, University of Massachusetts, Lowell,MA 01854, USA

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Michael R Hamblin

* Author for correspondence

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. .

Department of Dermatology, Harvard Medical School, Boston,MA 02115, USA

Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA

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Email the corresponding author at hamblin@helix.mgh.harvard.edu

Published Online:20 Feb 2014https://doi.org/10.2217/nnm.13.22

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Abstract

Background: Antimicrobial photodynamic therapy uses photosensitizers designed to bind to microorganisms and generate reactive oxygen species when illuminated with visible light. Materials & methods: We synthesized a highly water-soluble [70]fullerene monoadduct, C₇₀[>M(C₃N₆⁺C₃)₂]-(I^–)₁₀ (LC17), and bisadduct, C₇₀[>M(C₃N₆⁺C₃)₂][>M(C₃N₆C₃)₂] (LC18), both with a well-defined decacationic quaternary ammonium iodide moiety with ten positive charges per C₇₀ to give water solubility and bacterial binding. We determined the antimicrobial effects against human pathogens, Gram-positive (Staphylococcus aureus) and Gram-negative species (Escherichia coli and Acinetobacter baumannii) when activated by UVA or white light. Results: White light was more effective with LC17, while UVA light was more effective with LC18. Both compounds were effective in a mouse model of Gram-negative third-degree burn infections determined by bioluminescence imaging. Discussion & conclusion: We propose that the attachment of an additional deca(tertiary-ethylenylamino)malonate arm to C₇₀ allowed the moiety to act as a potent electron donor and increased the generation yield of hydroxyl radicals under UVA illumination.

Original submitted 13 June 2012; Revised submitted 10 January 2013; Published online 5 June 2013

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Financial & competing interests disclosure

This work was supported by NIH R01CA137108 and R01AI050875. T Dai was supported by an Airlift Research Foundation Extremity Trauma Research Grant (grant no. 109421) and a Basic Research Grant from the Orthopaedic Trauma Association (grant no. 2012-16), and FF Sperandio by CAPES Foundation, Ministry of Education of Brazil (grant no. 0310-11-5). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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