The main interest of the Zheng group is to develop clinically translatable technology platforms to combat cancer. Examples are:
- Porphysome nanotechnologyWe 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, porphysomes can directly chelate metal ions thus unlocking their potential to go far beyond biophotonics (e.g., positron emission tomography (PET), magnetic resonance imaging (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.
- Lipoprotein-like nanoparticlesLipoprotein-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) directly into the cytosol of cancer cells 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.
- Photodynamic molecular beaconsMolecular 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.
The role of the Chaperonin containing t-complex polypeptide 1, subunit 8 (CCT8) in B-cell non-Hodgkin's lymphoma.
Leuk Res. 2016 Jun;45:59-67
Bioconjug Chem. 2016 Jan 20;27(1):1-2
Bioconjug Chem. 2015 Feb 18;26(2):163-5
Biomimetic ApoE-Reconstituted High Density Lipoprotein Nanocarrier for Blood-Brain Barrier Penetration and Amyloid Beta-Targeting Drug Delivery.
Mol Pharm. 2016 Oct 4;:
Adv Drug Deliv Rev. 2016 Sep 2;
Porphysome nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model: a pilot study.
J Biomed Opt. 2016 Aug 1;21(8):84002
An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.
Cancer Res. 2016 Oct 1;76(19):5870-5880
Controlling Spatial Heat and Light Distribution by Using Photothermal Enhancing Auto-Regulated Liposomes (PEARLs).
Angew Chem Int Ed Engl. 2016 Aug 16;55(34):10003-7
Methods Mol Biol. 2016;1444:153-66
Biomed Opt Express. 2016 Mar 1;7(3):1089-99
Senior Scientist, Princess Margaret Cancer Centre
Core Lead, Techna Institute for the Advancement of Technology for Health (Techna)
Professor of Medical Biophysics, University of Toronto
Joey and Toby Tanenbam/Brazilian Ball Chair in Prostate Cancer Research
Professor, Institute of Biomaterials and Biomedical Engineering, University of Toronto
Professor, Department of Pharmaceutical Sciences, University of Toronto
Scientist, Joint Department of Medical Imaging, Mount Sinai Hospital, University Health Network, and Women’s College Hospital
Associate Editor, Bioconjugate Chemistry
Fellow, American Institute of Medical and Biological Engineering (AIMBE)