PLGA encapsulated porphyrin nanoparticles as activateable photodynamic therapy and imaging agents

ORGN 171

Jason R. McCarthy, jason_mccarthy@hms.harvard.edu, J. Manuel Perez, and Ralph Weissleder. Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, 149 13th St. Rm 5404, Charlestown, MA 02129
Intermolecular quenching of the excited states of porphyrins and chlorins can occur when the molecules are brought into close proximity (i.e. at high concentrations). We have found that encapsulation of meso-tetraphenylporphyrin, meso-tetraphenyldiethoxymorpholinochlorin, and meso-tetraphenylporpholactol within biodegradeable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (80-120 nm) causes quenching of the fluorescence emission of these chromophores in aqueous media. In media containing lipid, a time-dependant increase of emission intensity is observed. When these particles are incubated with cells (9L), they are rapidly internalized and show increased fluorescence over time. This may indicate the leaching out of the chromophore into adjacent lipophilic membranes. These nanoparticles are further useful in photodynamic therapy, as they are non-phototoxic until they are internalized by the cell and activated. As few as 25% of cells remain viable after only 3 h incubation time and light treatment.