Porphysome Nanotechnology: Discovery, clinical translation and beyond
Department of Medical Biophysics
University of Toronto
November 17, 2016
Abstract: Porphyrins are aromatic, organic, light-absorbing molecules that occur abundantly in nature, especially in the form of molecular self-assemblies. In 2011, we first discovered ‘porphysomes’, the self-assembled porphyrin-lipid nanoparticles with intrinsic multimodal photonic properties (Nature Materials 2011). The high-density porphyrin packing in bilayers enables the absorption and conversion of light energy to heat with extremely high efficiency, making them ideal candidates for photothermal therapy and photoacoustic imaging. Upon nanostructure dissociation, fluorescence and photodynamic activity of porphyrin monomers are restored. In addition, metal ions can be directly incorporated into the porphyrin building blocks of the preformed porphysomes thus unlocking their potential for PET and MRI. By changing the way porphyrin-lipid assembles, we developed HDL-like porphyrin nanoparticles (<20nm), porphyrin microbubbles (~2um), giant porphyrin vesicle (~100um), hybrid porphyrin-gold nanoparticles and metal chelating nanotexaphyrins. By mimicking light harvest systems in photosynthetic bacteria, we introduced high-ordered porphyrin aggregates into supramolecular assemblies, resulting unprecedented photonic properties (e.g., reversible photoacoustic nanosensors). Such optical properties are also responsible for our discovery of the ultrasound-induced microbubbles-to-nanoparticle conversion phenomenon (Nature Nano 2015), which may open the door to bypass the enhanced permeability and retention effect when delivering drugs to tumors. We have now validated porphysome’s multimodal theranostic utilities in different cancer types (head & neck, lung, pancreatic, prostate, brain and ovarian cancers, as well as lymph node and bone metastases), different tumor models (subcutaneous, orthotopic, chemically-induced and human primary xenografts) as well as different animal species (mice, rats, hamsters and rabbits). The effort of moving porphysomes towards first-in-human use is on the way. In summary, the simple yet intrinsic multimodal nature of porphysomes represents a new nanomedicine paradigm and also confers its high clinical translation potential.