Molecular Imaging and Minimally Invasive Therapy Laboratory

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Nanoparticle drug/gene delivery systems

The focus of our lab is to engineer versatile drug delivery systems (DDSs), such as microcapsules, nanoparticles, liposomes and microbubbles that can be targeted and delivered to specific tissues or organs. The as fabricated DDSs can be used to encapsulate genes, cells, enzymes, small peptides,  and active drugs. In particular, we also focus on the design of novel controlled drug release systems that can be triggered externally (magnetic field, microwave, ultrasonic exposure or light irradiation) or internally (enzymes, pH, MMP) to modulate the drug release property. It is our aim to expand the applications of nanotechnology ranging from the delivery of small molecules (e.g. chemotherapeutic drugs, phototherapeutic agents and imaging agents) to essential biological molecules such as proteins and genes across complex barriers for e.g. blood-brain barrier, the intestine, the lung and the skin in the body.

1. Liposomal nanohybrid cerasomes for drug delivery applications

Both liposomes and silica nanoparticles (NPs) have been widely investigated in the field of medicine to promote therapeutic efficacy by reducing drug dosage and eliminating toxicity. Despite the excellent biocompatibility, liposomes have not attained their full potential so far as drug and gene delivery vehicles due to the insufficient morphological stability and large-scale industrial production.

Bone tissues are composed of organic and inorganic hybrid composites with extremely high stability. Inspired by this, we have designed a novel hybrid composite named Cerasome, it possess a liposomal bilayer structure while with an atomic layer of inorganic polyorganosiloxane networks on its surface by molecularly designed lipidic organoalkoxysilane. These are prepared using a sol-gel method and self-assembly process based on the cerasome forming lipid of N-[N-(3-triethoxysilyl)propylsuccinamoyl]-dihexadecylamine that we designed. Such unique and stable structure provides immense opportunities to cerasomes in expanding roles as gene carriers, drug delivery systems, other several biomedical applications and biological energy transfer. We evaluated that the cellular uptake of cerasomes which is a concentration-, time-, and energy-dependent process mediated by a process of clathrin-mediated endocytosis, and can be loaded with hydrophilic, hydrophobic, as well as amphiphilic drugs without altering their morphological stability. In comparison with conventional liposomes or silica NPs, cerasomes take a number of advantages, including remarkably high mechanical stability and biocompatibility. Meanwhile, like silica NPs, the silanol groups located on the exterior surface of cerasome can be functionalized to allow the easy bioconjugation of monoclonal antibodies, folic acids or other specific molecules with silane-coupler chemistry to achieve targeted drug delivery. Cerasome is a novel drug delivery system with independent intellectual property rights, and on the account of its simple preparation techniques and easy industrialization process, it provides a brand-new technical platform for the research, development, application and promotion for the pharmaceuticals industry in China.

2.Hybrid bicelles -- lipid bilayer nanodiscs

Currently, about 40% of marketed drugs and more than 80% of new drugs in research and development are hydrophobic compounds, and their poor water-solubility greatly limits their clinical applications. Therefore, improving the solubility of hydrophobic drugs is a key issue to the pharmaceutical industry. Our group developed a novel silica-lipid precursor which can form hybrid bicelles in combination with 1,2-Dihexanoyl-sn-glycero-3-phosphochocholine(DHPC). Such bicelles can be employed to encapsulate hydrophobic anticancer drugs such as paclitaxel and 10-hydroxycamptothecine. After incorporating certain amount of PEG modified phospholipid, the circulating duration of the hybrid bicelles can be prolonged, meanwhile the drug release could be manipulated. Silanol groups on the surface of the bicelles can be conjugated with targeting ligands such as folate, thus effectively increase the tumor accumulation of nanodrugs, further enhancing their therapeutic efficacy.

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