Active Nanocarriers for Cancer BioDelivery

Time: 14:00~16:00

Date: Jan. 26th, 2010
Location: The Institute for Advanced Materials and Nano Biomedicine (iNANO), 67 Chifeng Road
Reporter: Youqing Shen

Task-specific biodelivery requires active nanocarriers that can respond to their environments. Cancerous cells overexpress membrane-associated multidrug resistance and have many intracellular drug-resistance mechanisms that limit cytosolic drugs’ access to the nucleus, causing low chemotherapeutic efficacy. To overcome the drug resistance for high therapeutic efficacy, we developed active nanocarriers including fast-release nanoparticles and nuclear localizing nanoparticles and polymer-drug conjugates for cancer drug delivery. Fast-release nanoparticles can quickly release the carried drug into the cytosol so that all the drug molecules are immediately available to overwhelm the cancer cell’s intracellular drug resistance mechanisms. Most cancer chemotherapeutic drugs target nuclear DNA to cause DNA damages and thereby induce cell death (apoptosis). Thus, drug carriers capable of localizing and directly releasing drugs into the nucleus would circumvent both the membrane-associated multidrug resistance and the intracellular drug-resistance mechanisms, leading to a high therapeutic efficacy. Accordingly, active nuclear localizing nanoparticles (ANLNs) and polymer-drug conjugates (ANLCs) were developed using a charge-reversal technique for in vivo nuclear delivery of DNA-toxins. Furthermore, cancer cells can alter their DNA to resist apoptosis. Cancer gene therapy is a promising approach to overcoming such resistance. Its bottleneck is efficient gene delivery. Polymer gene delivery is a safe alternative to viral gene delivery but suffers low transfection efficiency. We developed virion-mimicking nanocapsules, in which free plasmids are encapsulated as the core with a hydrophobic middle layer for protection and a PEG outer layer for stealth properties for gene delivery to cancer. This type of artificial virus is very effective in gene transfection compared with PEI mediated gene delivery, and promising for in vivo cancer gene delivery. The recent developments in prodrug nanocarriers and dendrimers for drug delivery will also be discussed.

Youqing Shen obtained his BS in chemistry in 1991 and Doctor of Science in polymer science supervised by prof. Zhiquan Shen in 1995 from Zhejiang University. His thesis won the first “National Outstanding Dissertation Award” in 1999. He obtained a PhD degree in Chemical Engineering in 2001 from McMaster University in Canada. After working one year at Akzo Nobel as a research scientist, he moved to the University of Wyoming as an assistant professor in late 2002. He was early promoted as an associate professor with tenure in 2007. He returned Zhejiang University in 2008 as a fulltime Quishi chair professor and Director of Center for Bionanoengineering. He won the National Distinguished Young Scholar Award from National Natural Science Foundation of China in 2008. He has published more than 110 highly ranked papers in Macromolecules, Angew Chem and JACS etc. His research interest is synthesis of nanostructured polymers for bioengineering.


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