title: Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections.
abstract: OBJECTIVE
  Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds.
  
  
  METHODS
  We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 × 10(7) cells) and Pseudomonas aeruginosa (5 × 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm).
  
  
  RESULTS
  In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01).
  
  
  CONCLUSIONS
  These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114, USA.
authors.forename: Zongshun
authors.initials: Z
authors.lastname: Lu
authors.forename: Tianhong
authors.initials: T
authors.lastname: Dai
authors.forename: Liyi
authors.initials: L
authors.lastname: Huang
authors.forename: Divya B
authors.initials: DB
authors.lastname: Kurup
authors.forename: George P
authors.initials: GP
authors.lastname: Tegos
authors.forename: Ashlee
authors.initials: A
authors.lastname: Jahnke
authors.forename: Tim
authors.initials: T
authors.lastname: Wharton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D000818:Animals; D037741:Fullerenes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014946:Wound Infection / Q000188:drug therapy*
chemical_list: D037741:Fullerenes; D017319:Photosensitizing Agents