NanoJanus and Nanosatellite Assembly for Biomolecular Delivery and Cancer Therapeutics

Nanotechnology has been utilized widely in medical fields to improve the treatment and diagnosis of several diseases. One of the key players to drive medical nanotechnology forward is nanoparticles, which have been intensively studied and used as a tool for imaging, drug delivery, and disease treatments. Gold and iron oxide, undoubtedly, are on the short list of the nanoparticles used in medical nanotechnology due to their biocompatibility, tunable surface, and unique physico-chemical properties. In this dissertation, we developed novel nanostructures using gold, iron oxide nanoparticles and polymers for various applications including Janus motors, vaccine delivery, and controlled drug release. We generated an asymmetrical Janus nanostructure using thermo-cleavable polymer, gold, and iron oxide nanoparticles for photothermal enhancement and nano motors through an active rotational motion. Gold/iron oxide Janus nanoparticles (JNS) are developed by a seed-mediated self-assembly using a thermo-cleavable polymer facilitating the process. The formed JNS strongly displays an asymmetrical photothermal effect to activate a rotational motion and enhances photothermia resulting in significant cell killing effects under weak near-infrared (NIR) light exposure. In addition, the JNS displays distinct active rotational motion under NIR laser light due to the temperature gradient at its surface, which can be used potentially as Janus motors for drug delivery in the future. We next harnessed the same thermo-cleavable polymer used in JNS formation for controlled drug release under NIR laser light irradiation. The iron oxide nanoparticles (IONP) were first encapsulated in the thermo-cleavable polymeric micelles with doxorubicin (Dox), a chemotherapeutic drug. After NIR trigger, the polymer is cleaved due to heat transfer from the IONP resulting in the release of doxorubicin from the micelles. This study demonstrated that the thermo-cleavable polymer could be used as a smart material for controlled drug release. We also generated another type of secondary structure, a “gold/iron oxide nanosatellite”, using poly (- methacryloxypropyl trimethoxysilane) -b- poly (ethylene oxide) polymer (MPS-b-PEO). This nanosatellite structure, in which IONP is a central core and surrounded by multiple gold nanoparticles as satellites, is used for delivering antigens and an adjuvant for HPV+ head and neck cancer treatment. These nanosatellites deliver high surface density of E7/E6 oncogenic peptides and cyclic- guanosine-adenosine monophosphate (cGAMP) adjuvant to antigen presenting cells (APC) and further activate type I interferon (IFN-I) response. The nanosatellite vaccine also promotes antigen specific CD8+ T cells to infiltrate the tumors and inhibits tumor growth in an HPV+ head and neck tumor model when used as a single therapy or in combination therapy with an anti PD-L1 antibody. Nanosatellites offer many advantages for antigenic peptide and adjuvant delivery such as having a larger surface area, higher antigenic peptide density, higher cell uptake, and lower systemic elimination. This thesis presents the versatile developments and applications of gold/iron oxide nanostructures (Janus and Nanosatellite) which have advantages for drug and vaccine delivery in the future.PHDPharmaceutical SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/140893/1/kanokwas_1.pd