EAPSI: Nanoparticle design for controlled and efficient delivery of anti-cancer therapeutics

Decato Sarah, Madison WI

Investigators

Abstract

Cancer remains a leading cause of death worldwide. Chemotherapy is a potent treatment method; however, the efficient delivery of anti-cancer drugs remains a major barrier to successful treatment. Improvements have been achieved using nano-scale self-assembling particles, which can encase the drug to lessen side effects and to target cancerous tissue. The functionality of the nanoparticles is dictated by the design of the individual molecules comprising the assembly. In this research, fluorine-containing molecules have been designed to efficiently deliver anti-cancer drugs and to simultaneously enable magnetic resonance imaging (MRI), which can visualize nanoparticle behavior. The proposed molecules will be synthesized and evaluated at the University of Tokyo in Japan in collaboration with Dr. Kazunori Kataoka, whose expertise and equipment will greatly facilitate and strengthen this research project. Multifunctional polymers have been synthesized to address the challenge of targeted drug delivery towards improved chemotherapy. These polymers self-assemble into nanometer-sized micelles that can encapsulate anti-cancer agents, providing enhanced solubility and reduced systemic toxicity. This is achieved via a strategic polymer design including a symmetrical fluorinated segment to increase the stability of the assembly and to provide simultaneous 19F MRI capability. These dually functional particles can be applied to disease diagnosis and in vivo bioavailability analysis. In this research, targeting peptide ligands will be appended to the surface of the nanoparticles to facilitate penetration into cancer cells. Additionally, the behavior of the drug carriers in vitro (via cell toxicity and cell uptake assays) and in vivo (via intravital real-time confocal laser microscopy measurements) will be investigated. These experiments will elucidate key self-assembly interactions, which can then be leveraged to design more efficient and environmentally benign nanoparticles. This NSF EAPSI award is funded in collaboration with the Japan Society for the Promotion of Science.