Anti-microbial photodynamic therapy
View Patent ↗Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The key to these conjugates is a special spacer connecting at least one photosensitizer to a microorganism receptor (vector) which in turn binds selectively to the surface of a microorganism bringing about photo-destruction upon irradiation. Spacers having hydrophilic structure such as ethylene glycol units and amino carboxyl end capped ethylene glycol units must be used for linking the vector to the photosensitizer. In a preferred embodiment a spacer would have at least 3 ethylene glycol units and be end capped with a carboxyl group on one end and a amino group at the other end. The present invention effectively works to combat bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or at least nearby. Spacers of selected length and structure, in preferred embodiments, are used for linking the vector to the photosensitizer. These conjugate are found to be very effective in combating bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or a least nearby. A method of use is also provided.
1. A molecular conjugate comprising a mesopyropheophorbide-a and a targeting peptide, wherein said targeting peptide is SEQ ID NO: 1, and wherein the mesopyropheophorbide-a and targeting peptide are connected by a hydrophilic spacer comprising up to 45 atoms, at least three ethylene glycol units, an amino end cap and a carboxyl end cap.
2. The molecular conjugate of claim 1 , wherein said backbone spacer has a structure selected from the group consisting of:
3. The molecular conjugate of claim 1 , wherein said spacer is no longer than 21 atoms.
4. The molecular conjugate of claim 2 , wherein said spacer is
5. The molecular conjugate of claim 2 , wherein said spacer is
6. A method of inactivating or reducing microorganisms in at least one of blood, serum, plasma or saliva comprising the steps of:
selecting a molecular conjugate, according to claim 1 , with a peptide component targeting said microorganisms to be inactivated or reduced;
introducing said molecular conjugate to said at least one of blood, serum, plasma or saliva;
allowing time for said molecular conjugate to accumulate in said targeted microorganisms; and,
irradiating said targeted microorganisms with an appropriate wavelength to activate said molecular conjugate to destroy said targeted microorganisms.
7. The method of claim 6 , wherein said targeted microorganisms are Gram-negative or Gram-positive microorganisms.