Magneto-plasmonic nanoparticle platform for detection of rare cells and cell therapy
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Magnetic and plasmonic properties combined in a single nanostructure provide a synergy that is advantageous in a number of biomedical applications, such as contrast enhancement in multimodal imaging, simultaneous capture and detection of circulating tumor cells, and photothermal therapy of cancer. These applications have stimulated significant interest in development of magneto-plasmonic nanoparticles with optical absorbance in the near-infrared region and a strong magnetic moment. In this dissertation, we addressed this need to create a novel immunotargeted magneto-plasmonic nanoparticle platform. The nanostructures were synthetized by self-assembly of primary 6 nm iron oxide core-gold shell particles, resulting in densely packed spherical nanoclusters. The close proximity of the primary particles in the nanoclusters generates a greatly improved response to an external magnetic field and strong near-infrared plasmon resonances. A procedure for antibody conjugation and PEGylation to the hybrid nanoparticles was developed for biomedical applications which require molecular and biocompatible targeting. Furthermore, we presented two biomedical applications based on the immunotargeted hybrid nanoparticle platform, including circulating tumor cell (CTC) detection and cell-based immunotherapy of cancer. In the CTC detection assays, rare cancer cells were specifically targeted by antibody-conjugated nanoparticles and efficiently separated from normal blood cells by a magnetic force in a microfluidic chamber. The experiments in whole blood showed capture efficiency greater than 90% for a variety of cancers. We also explored photoacoustic imaging to detect nanoparticle-labeled CTCs in whole blood. The results showed excellent sensitivity to delineate the distribution of hybrid nanoparticles on the cancer cells. Thus, these works paves the way for a novel CTC detection approach which utilizes immunotargeted magneto-plasmonic nanoclusters for a simultaneous magnetic capture and photoacoustic detection of CTCs. In another application, we introduced a novel approach to label cytotoxic T cells using the magnetic nanoparticles with an expectation to enhance T cell recruitment in tumor under external magnetic stimulus. A series of in vitro experiments demonstrated highly controllable manipulation of labeled T cells. Thus, these results highlight the promise of using our nanoparticle platform as a multifunctional probe to manipulate and track immune cells in vivo and further improve the efficacy of cell-based cancer immunotherapy.