Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships

Abstract

Photosensitive dyes or photo sensitizers (PS) in combination with visible light and oxygen produce reactive oxygen species that kill cells in the process known as photodynamic therapy (PDT). Antimicrobial PDT employs PS that is selective for microbial cells and is a new treatment for infections. Most antimicrobial PS is based on tetrapyrrole or phenothiazinium structures that have been synthesized to carry quaternary cationic charges or basic amino groups. However we recently showed that cationic-substituted fullerene derivative were highly effective in killing a broad spectrum of microbial cells after illumination with white light. In the present report we compared a new group of synthetic fullerene derivatives that possessed either basic or quaternary amino groups as antimicrobial PS against Gram-positive (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli) and fungi (Candida albicans). Quantitative structure-function relationships were derived with LogP and hydrophilic lipophilic balance parameters. Compounds with non-quaternary amino groups tended to form nanoaggregates in water and were only effective against S. aureus. The most important determinant of effectiveness was an increased number of quaternary cationic groups that were widely dispersed around the fullerene cage to minimize aggregation. S. aureus was most susceptible; E. coli was intermediate, while C. albicans was the most resistant species tested. The high effectiveness of antimicrobial PDT with quaternized fullerenes suggest they may have applications in treatment of superficial infections (for instance in wounds and burns) where light penetration into tissue is not problematic.

Photodynamic Therapy of Infectious Disease Mediated by Functionalized Fullerenes

“…Fullerenes can also be modified with the trapping of additional metal atoms within their cage-like structure; these particular compounds are known as "endohedral fullerenes." One of the major advantages of this is that it allows for significant modification of the fullerene molecule, overcoming some of its major disadvantages and allowing tailor-engineering of the fullerene (Ikeda et al, 2009;Mizuno et al, 2011). Kässerman and Kempf (1997) and Hirayama et al (1999) are among several groups that studied the use of photoactivated fullerenes against viruses in vitro, and both found that fullerenes mainly inactivated viruses through their production of singlet oxygen, which is virucidal.…”

Biological activity of fullerenes - reality and prospects

“…Изучение связи структуры функционализиро-ванных фуллеренов с их антимикробной фотодина-мической активностью было проведено K. Mizuno et al [33]. Применение этих соединений возможно при лечении кожных инфекций, например ран и ожо-гов, где проникновение облучения в ткань не являет-ся проблемой.…”

Nanotextiles- A Broader Perspective

“…The use of the silver and gold particles [73] enables the odour resistance and anti bacterial and antifungal properties [74,75]. The titanium dioxide is for the uv-protection and nano whiskers for the water repellent property.…”