TECHNOLOGY BRIEF
395 Pine Tree Road, Suite 310 Ithaca, NY 14850 P: 607-254-4698 F: 607-254-5454 E: cctecconnect@cornell.edu www.cctec.cornell.edu Inventors: Michael King Xiaoyan Yin Kuldeepsinh Rana Varun Ponmudi Andrew Hughes Patents: Filed Contact: Jeff Fearn, PhD Sr. TCLO Office: 607-254-4502 E-mail: jcf55@cornell.edu Cornell Ref: D-4920/D-4968/D-4973
Link to Origanal PDFFunctionalized Liposomes for Targeting and Treatment of Diseases
CCTEC D-4920/D-4968/D-4973
Invention Summary
Several technologies in combination create a novel method to target and/or treat cells, such as metastasized cancer cells.
This invention involves the use of functionalized liposomes. These liposomes may be functionalized with an adhesion molecule such as selectin alone or in combination with other entities. These liposomes may also have incorporated within it molecules such as siRNA or drugs.
Cornell researchers have shown proof of principle by functionalizing the surface of the liposome with selectin, which can interact with certain cancer cells. These liposomes can also have incorporated on their surface or into them:
1. FUT3 siRNA – functions by decreasing protein expression of fucosyltransferase 3 of cancer cells, thus inhibiting metastasis.
2. Doxorubicin – a cancer-killing agent that directly destroys cancer cells.
3. TRAIL– interacts with the Death Receptor on cancer cells, initiating their death.
Cornell inventors have also used functionalized halloysite nanotubes that project from the surface of the microtube they coat, increasing the available surface area and thus significantly enhancing the capture of circulating tumor cells and binding them. There is no effect on the viability of these cells, enabling their use for in vitro studies on the characteristics of the cancer and experimental drug therapies.
Background Information
Most cancer-related deaths are associated with the formation of metastatic tumors. One problem with targeted drug delivery to cancer cells is that the cancer cells have similarities with some normal cells, and are thus compromised during the course of treatment. A more targeted approach is needed to preserve the integrity of normal, healthy human cells while inducing apoptosis in cancer cells that have metastasized.
Technical Merits:
• Liposomes may be adapted to different cancers by functionalizing with the appropriate binding molecule, or to other sites, such as areas of inflammation.
• Functionalized liposomes can be used alone or in conjunction with other therapies.
• Halloysite nanotubes increase surface area by projecting from surface.
• Potential to use these novel therapies in vivo.
Potential Commercial Applications:
• Treatment of metastasized cancer using FUT3 siRNA.
• Treatment of other cancers, inflammation and other targets.
• Screening tool for drug therapies.
• Research tool.
Potential Advantages:
• Metastasized CTCs are specifically targeted without harm to normal cells.
• Can functionalize liposomes to specifically target cell of interest.
• With halloysite nanotubes, the viability of CTCs is preserved, enabling the cells to be cultured
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Use of Naturally Occurring Halloysite Nanotubes for Enhanced Capture of Flowing Cells
Andrew D. Hughes and Michael R. King*
Abstract
The development of individualized treatments for cancer can be facilitated by more efficient methods for separating cancer cells from patient blood in such a way that they remain viable for live cell assays. We have previously shown that immobilized P-selectin protein can be used on the inner surface of a microscale flow system to induce leukemic cells and leukocytes to roll at different velocities and relative fluxes, thereby creating a means for rapid cell fractionation without inflicting cellular damage. In this study, we explore a method to more efficiently capture leukemic and epithelial cancer cells from flow by altering the nanoscale topography of the inner surface of P-selectin-coated microtubes. This functionalized topography is achieved by attaching naturally occurring halloysite nanotubes to the microtube surface via a monolayer of poly-l-lysine), followed by functionalization with recombinant human selectin protein. We have found that halloysite nanotube coatings promote increased capture of leukemic cells and have determined the key parameters for controlling cell capture under flow: halloysite content and selectin density. Ultimately, selectin-functionalized nanotube coatings should provide a means for enhanced cancer cell isolation from whole blood and other mixtures of cells.
The development of individualized treatments for cancer can be facilitated by more efficient methods for separating cancer cells from patient blood in such a way that they remain viable for live cell assays. We have previously shown that immobilized P-selectin protein can be used on the inner surface of a microscale flow system to induce leukemic cells and leukocytes to roll at different velocities and relative fluxes, thereby creating a means for rapid cell fractionation without inflicting cellular damage. In this study, we explore a method to more efficiently capture leukemic and epithelial cancer cells from flow by altering the nanoscale topography of the inner surface of P-selectin-coated microtubes. This functionalized topography is achieved by attaching naturally occurring halloysite nanotubes to the microtube surface via a monolayer of poly-l-lysine), followed by functionalization with recombinant human selectin protein. We have found that halloysite nanotube coatings promote increased capture of leukemic cells and have determined the key parameters for controlling cell capture under flow: halloysite content and selectin density. Ultimately, selectin-functionalized nanotube coatings should provide a means for enhanced cancer cell isolation from whole blood and other mixtures of cells.
Additional Information (publications, web sites, and patent links)
Supporting Documents
- Technology brief (117KB PDF)
Innovators & Portfolio
- Michael King | more technologies from Michael King
- Andrew Hughes
Licensing Contact
Jeff Fearn, Senior Technology Commercialization and Liaison Officerjcf55@cornell.edu
607-254-4502
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NaturalNano, Inc. (OTCBB:NNAN.OB ) (www.naturalnano.com) Halloysite Nanotubes
