Single-Step Manufacture of Affinity Nanodiscs for Drug Delivery

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This project is aimed to develop a novel method that enables the mass production of lipid-based affinity nanodiscs in a simple but very effective manner. Manufacturing of affinity nanocarriers for targeted drug delivery has attracted significant attention in the field of nanotechnology. One of the most widely studied nanocarriers is antibody-functionalized liposomes. However, the synthesis of drug-loaded affinity liposomes usually requires time-consuming and multiple-step process, resulting in costly mass production. Moreover, the aqueous core within liposomes is not favorable for encapsulating hydrophobic drugs. In this project, nucleic acid aptamers and hydrophobic drugs will be incorporated to the self-assembled lipid-based nanodiscs in aqueous solutions. It is expected that such vehicles have the capability of targeting specific cells and carrying a large amount of hydrophobic molecules. Preliminary studies have shown that stable nanodiscs are attainable and the aptamers are functional after chemical conjugation. Based on the compelling results, this project includes (1) synthesizing and characterizing the novel affinity nanodiscs, (2) modeling the growth kinetics and dynamic interactions of the nanodiscs, and (3) understanding the biological functions of the affinity nanodiscs. The anticipated outcomes of this interdisciplinary study are to provide insights into the kinetics and thermodynamics of molecular self-assembly and to develop a transformative method for preparing affinity nanocarriers for hydrophobic drugs. This research will lead to several scientific and economic impacts. First, the one-step manufacturing of the novel nanodiscs will greatly reduce the cost of mass production, making the relevant targeted chemotherapy more affordable to the general public. Second, since more than 40 percent of the new anti-cancer drugs are hydrophobic, this delivery platform will pave a new way of delivering hydrophobic drugs especially for cancer chemotherapy. Third, the data to be generated will further enrich the knowledge of nanotechnology, molecular recognition, and colloidal science. The broader educational impacts of this project will also be evident in our strong commitment to education and human resource development. First, this project will provide students with a unique interdisciplinary environment to learn nanotechnology, drug delivery, colloidal science, biomolecular engineering, kinetic analysis, and mathematical modeling. All participating students will have modularized scientific questions to study and will discuss their research findings in joint group meetings. The students will be able to not only acquire hands-on research skills, but also learn analytical, communication, collaboration, and innovation skills. In addition, the PIs will incorporate the results from this research into their teaching courses ("structural characterization of soft materials" and "drug delivery"). Second, the PIs will continuously participate in the outreach programs established at UConn. These outreach efforts will raise K-12 students' interests in science and engineering and facilitate the transfer of the novel bench work to biopharmaceutical industries. Third, the research findings will be widely disseminated through publications in peer-refereed journals and presentations at professional conferences.