题目：From nano to micro, and back: explore new frontiers of cancer imaging and therapy
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. 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 disruption, fluorescence and photoreactivity of free porphyrins are restored to enable low background fluorescence imaging and activatable photodynamic therapy. Metal ions can be directly incorporated into the porphyrin building blocks of the preformed porphysomes thus unlocking their potential for PET and MRI. Later, we developed different porphyrin microstructures including porphyrin-shell microbubbles for trimodal (ultrasound/photoacoustic/fluorescence) imaging. Upon ultrasound exposure, porphyrin microbubbles form nanoparticles that possess the same optical and therapeutic properties as the original microbubble, thus providing an interesting opportunity to overcome the Achilles’ heel of cancer nanotechnology, where the over reliance of the enhanced permeability and retention effect has consistently resulted in promising efficacy in mouse models but poor clinical track record. By closing the nano-micro-nano loop, the simple yet intrinsic multimodal nature of porphyrin self-assembly represents a new frontier in cancer imaging and therapy.
Dr. Zheng is a Professor of Medical Biophysics, Biomedical Engineering and Pharmaceutical Sciences at the University of Toronto, a Senior Scientist, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research at the Princess Margaret Cancer Center, and the Scientific Lead for Nanotechnology and Radiochemistry at the Techna Institute. He received his PhD in 1999 from SUNY Buffalo in Medicinal Chemistry. Following two year postdoctoral training in photodynamic therapy at the Roswell Park Cancer Institute, he joined the University of Pennsylvania in 2001 as an Assistant Professor of Radiology, where he established the molecular imaging chemistry program and introduced photodynamic molecular beacons and lipoprotein-like nanoparticles. Since moving to Canada in 2006, his research has been focused on developing clinically translatable technology platform to combat cancer. His lab discovered porphysome nanotechnology (Nature Materials 2011) that was named one of the “top 10 cancer breakthroughs of 2011” by the Canadian Cancer Society. His lab also discovered that on exposure to low-frequency ultrasound porphyrin microbubbles form nanoparticles that possess the same optical and therapeutic properties as the original microbubble, which can be used simultaneously for imaging and drug delivery (Nature Nanotechnology 2015). Dr. Zheng is an Associate Editor for the Bioconjugate Chemistry.