Engineering and characterizing nanoparticles for cancer targeting

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1159967/ Kokkoli This NSF award by the Interfacial Processes and Thermodynamics and the Biotechnology, Biochemical and Biomass Engineering programs supports the development of novel aptamer functionalizes stealth liposomes that bind to a new cell surface molecule (fractalkine) on cells associated with cancer and inflamation. Aptamers are short single-stranded oligonucleotides. They are chemically produced, have the capability of binding with high affinity and specificity a variety of different targets, and have been shown to be useful as therapeutic agents and diagnostic tools. Their affinities are often comparable to those observed for monoclonal antibodies, and are significantly higher compared to those of peptides. As aptamer-amphiphiles, aptamers attached to a hydrophobic tail, they can assemble with other lipids into liposomes that can be used as targeted nanoparticles to treat different diseases, including cancer. Researchers will engineer and characterize in vitro fractalkine targeted stealth liposomes and evaluate their binding affinity and specificity for fractalkine expressing colon cancer cells, as well as internalization and trafficking by these cells. These experiments will identify the optimal aptamer concentration that will be used for the design of the targeted delivery system. The PI will then characterize the aptamer functionalized nanoparticles in vivo and evaluate their ability to reach the tumor site selectively in a murine model of colorectal cancer while avoiding health areas, as well as its efficacy and toxicity. For this task the nanoparticles will be loaded with doxorubicin. The innovative aspect of this proposal is the proposed use of the novel molecule, fractalkine, as a target for the delivery of nanoparticles that encapsulate a therapeutic payload. The proposed work will be of fundamental but also of practical significance as the engineered aptamer-functionalized stealth liposomes that will result from this study can be used as targeting nanoparticles in different applications and encapsulate different loads of interest.The PI integrates her research with her educational plan. One educational activity focuses on targeting underrepresented minority students at the Saint Paul College, A Community & Technical College (with a large representation of a wide range of minority populations) with the focus of exposing them to the research performed in the PI's lab, and motivating them to transition into four-year colleges and universities. The PI is currently collaborating, and will continue to do so in the future, with MRSEC. Through MRSEC the PI will be hosting during the summer high school teachers, and minority undergraduates from a nationwide pool of applicants, through a well established network of high schools, and minority undergraduates from a number of Minority Serving Institutions. To further attract underrepresented minority undergraduates in the her laboratory, the PI will be attending and presenting at the North Star STEM Alliance symposium. Furthermore, the PI has participated, and will continue to participate, in outreach activities organized by different organizations and societies with the goal of attracting and mentoring women in sciences and engineering (a long term goal for the PI). As part of this goal the PI is proposing to organize a seminar series in the Department of Chemical Engineering and Materials Science at theUniversity of Minnesota, entitled "Women Engineers in Academia and Industry" with monthly seminars given by women that will serve as positive role models for the female students and postdocs.