Porphysome Nanotechnology: Explore New Frontiers of Cancer Imaging and Therapy

Porphyrins are the endogenous chromophores of nature such as hemes in red blood cells and chlorophylls in green plants. Porphyrins and porphyrin-like molecules are well known photosensitizers for photodynamic therapy and fluorescence imaging, and there has been rekindled interest for nuclear medicine given their radioisotope chelating ability. In the course of examining porphyrin self-quenching in liposomes to explore their potential use as activatable photosensitizers, we discovered ‘porphysomes’, the first all-organic nanoparticles with intrinsic multimodal photonic properties. They are self-assembled from porphyrin-lipid building blocks to form liposome-like bilayer vesicle (~100 nm diameter). The very high porphyrin packing density (>80,000 per particle) results in both ‘super’-absorption and structure-dependent ‘super’-quenching, which, in turn, converts light energy to heat with extremely high efficiency, giving them ideal photothermal and photoacoustic properties that are unprecedented for organic nanoparticles. Upon porphysome nanostructure dissociation, fluorescence of free porphyrins is restored to enable low background fluorescence imaging. In addition, metal ions (e.g., radioactive copper-64) can be directly incorporated into the porphyrin building blocks of the preformed porphysomes thus unlocking their potential for PET, MRI and radiation therapy. As a result of their organic nature, porphysomes were biodegradable in vivo and induced minimal acute toxicity in mice with high intravenous doses. In a similar manner to liposomes, porphysomes can be easily scaled up via commercial extrusion techniques and the large aqueous core of porphysomes could be passively or actively loaded with drugs, opening up a new avenue for image-guided drug delivery. By changing the way porphyrin-lipid assembles, we developed ultra small porphyrin nanodiscs (<20nm) and large porphyrin shell microbubbles (~2um), expanding the purview of porphyrin nanophotonics. Compared with classical “all-in-one” nanoparticles containing many functional modules, the simple yet “one-for-all” nature of porphysomes represents a novel approach to the design of multifunctional nanoparticle and confers high potential for clinical translation.