The main interest of the Zheng group is to develop clinically translatable technology platforms to combat cancer. Examples are:
1. Porphysome nanotechnology: We recently discovered porphysomes, the first-in-class, all organic and targetable nanoparticles with intrinsic multimodal photonic properties (Nature Materials
2011). These 'one particle to rule them all' nanoparticles (editorial, Nature Methods
, 2011) were identified by the Canadian Cancer Society as one of the top-ten breakthroughs in cancer research in 2011. They are self-assembled from porphyrin-lipid building blocks to form liposome-like nanoparticles (~100 nm diameter). The porphyrin packing density is so high (>80,000 per particle) that they absorb and convert light energy to heat with extremely high efficiency, making them ideal candidates for photothermal therapy and photoacoustic imaging. In addition, the large aqueous core of porphysomes could be loaded with drugs; upon porphysome bilayer disruption, fluorescence imaging could be enabled. Compared with any other photonic nanomaterials, porphysomes have considerably lower translational hurdles owing to their a) robust scale up following proven liposome technology, b) extremely low systemic toxicity, and c) biodegradable in vivo. Further, porphysome can directly chelate metal ions thus unlocking their potential to go far beyond biophotonics (e.g., PET, MRI and radiation therapy). Together, the simple yet intrinsic multimodal nature of porphysomes not only confers high potential for clinical translation but also represents a novel principle for designing multifunctional nanoparticles.
2. Lipoprotein-like nanoparticles: Lipoprotein-like nanocarriers are a novel class of biocompatible, biodegradable and multifunctional nanoparticles based on chemically modified lipoproteins or artificially engineered lipoprotein mimetics. In particular, the ultra small HDL-like nanopaticles are capable of delivering therapeutic molecules (siRNA or drugs) into the cytosol of cancer cells directly thus bypassing the detrimental endosomal trapping for cancer therapeutics. DLVR Therapeutics, a new Ontario start-up company was recently created to commercialize this novel nanotechnology.
3. Photodynamic molecular beacons: Molecular beacons are target-activatable probes that use the fluorescent resonance energy transfer principle to control their fluorescence emission in response to specific biological stimuli. We have extended this exclusive imaging utility to the concept of activatable photodynamic therapy. These therapeutic beacons usually comprise a disease-specific linker (e.g., peptides or oligonucleotides), a photosensitizer and a quencher. This configuration allows the photosensitizer's phototoxicity to be silenced until the specific linker-target interactions (e.g., protease-mediated linker cleavage or nucleic acid hybridization-induced linker opening). Thus, the beacons can achieve a very high level of PDT treatment selectivity by destroying only the targeted cancer cells, while leaving non-targeted (normal) cells unharmed.
- Professor of Medical Biophysics, University of Toronto
- Joey and Toby Tanenbam/Brazilian Ball Chair in Prostate Cancer Research
- Professor, IBBME (cross appointment), University of Toronto
- Professor, Department of Pharmaceutical Sciences (cross appointment), University of Toronto
- Co-lead, Nanotechnology and Radiochemistry, Techna Institute