Antimicrobial Photodynamic Inactivation at the Nanoscale

One of the biggest health problems facing the world today is the inexorable rise of multi-antibiotic resistance amongst a wide range of pathogens, including Gram-positive and Gram-negative bacteria and fungi. Antimicrobial photodynamic inactivation (aPDI) uses visible/NIR excitation of a photosensitizer to produce the reactive oxygen species (ROS) singlet oxygen (Type 2) and hydroxyl radicals (Type1) that are both highly toxic to microbial cells. If the photosensitizer and the light are introduced into the infected area the selectivity is excellent. This presentation will describe how nanotechnology can be applied to a real medical problem.

Fullerenes (C60, C70 and C84) can be functionalized by attachment of deca-quaternized polycationic chains to enhance water solubility and binding to bacteria. Light-harvesting antennae and deca-tertiary amine chains can also be covalently attached to the cage, which serve as additional sources of electrons in a Type 1 electron transfer mechanism.

Titania photocatalysis using P25 TiO2 25-nm diameter nanoparticles can act as broad-band gap semi-conductors, and upon excitation with UVA light (360 nm) can carry out electron transfer reactions producing hydroxyl radicals (and also singlet oxygen).

Our laboratory has discovered that addition of simple inorganic salts can potentiate aPDI by several orders of magnitude, and may even allow oxygen-independent photoinactivation to take place. Potassium iodide is the most powerful and clinically relevant salt. Other inorganic salts such as sodium azide, potassium thiocyanate, potassium selenocyanate, potassium bromide and sodium nitrite also produce increased killing of a broad range of pathogens by up to one million times. The underlying photochemical mechanisms will be discussed.

 

Michael Hamblin is a Principal Investigator at the Wellman Center for Photomedicine at Massachusetts General Hospital, an Associate Professor of Dermatology at Harvard Medical School and a member of the Affiliated Faculty of Harvard-MIT Division of Health Science and Technology. He was trained as a synthetic organic chemist and received his PhD from Trent University in England. He joined Wellman Labs in 1994. He worked initially in targeted photodynamic therapy (PDT) and prepared and studied conjugates between photosensitizers and antibodies or targeted proteins and polymers of varying charge.