Targeted antimicrobial photodynamic therapy

Abstract

The present application relates generally to a method and a composition matter that provides a rapid and potent antimicrobial photodynamic inactivation (aPDI) of pathogenic bacteria that express high-affinity cell-surface hemin receptors (CSHRs) using Ga(III)-protoporphyrins IX (GaPpIX or Ga-PpIX). The invention provides an effective treatment option for infections of skin or body cavities that are accessible to visible-light irradiation, such as a handheld LED array emitting visible light (405 nm), especially for infections caused by Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), pathogenic staphylococci, Streptococcus mutans, S. pneumoniae, S. pyogenes, streptococci, corynebacteria, mycobacteria, and Bacillus anthracis.

We claim: 
     
         1 .- 13 . (canceled) 
     
     
         14 . A pharmaceutical composition for treatment of a topical infection caused by a bacterium expressing a high-affinity cell-surface hemin receptor in combination with a light comprising a photo sensitizer of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable diluents, excipients or carriers, wherein 
         M is a metal or coordinated metal ion; 
         R 1  is hydrogen, an alkyl, or a substituted alkyl; 
         R 2  is an alkyl, or a substituted alkyl; 
         R 3  is an acyl, alkenyl, α-hydroxyalkyl, aryl, or aromatic heterocycle, each of which is optionally substituted; and 
         R 4  is an alkyl, or a substituted alkyl. 
       
     
     
         15 . The pharmaceutical composition of  claim 14  further comprising a targeting protein or a nanoparticle. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein said nanoparticle is a silver or gold nanoparticle. 
     
     
         17 . The pharmaceutical composition of  claim 14 , further comprising an aminoglycoside antibiotic. 
     
     
         18 . The pharmaceutical composition of  claim 14 , wherein R 2  and R 4  are methyl; R 3  is vinyl; and R 1  is methyl or hydrogen. 
     
     
         19 . The pharmaceutical composition of  claim 14 , wherein M is a halo coordinated ion of magnesium, iron, manganese, cobalt, nickel, copper, zinc, and gallium. 
     
     
         20 . The pharmaceutical composition of  claim 14 , wherein said compound has formula (II) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable diluents, excipients or carriers. 
       
     
     
         21 . The pharmaceutical composition of  claim 14 , wherein said light is a visible or infrared light. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein said light is a visible light of max about 405 nm. 
     
     
         23 . The pharmaceutical composition of  claim 14 , wherein said infection is a topical skin, a body or an inner body cavity that is accessible to light irradiation. 
     
     
         24 . The pharmaceutical composition of  claim 14 , wherein said bacterium comprises  Staphylococcus aureus,  Methicillin-resistant  Staphylococcus aureus  (MRSA), vancomycin resistant  S. aureus  (VRSA),  S. epidermidis,  pathogenic staphylococci,  Streptococcus mutans, S. pneumoniae, S. pyogenes,  streptococci, corynebacteria, mycobacteria, and  Bacillus anthracis.