This Is AuburnElectronic Theses and Dissertations

Precision Medicine Based on Real-time Immune Status Profiling Utilizing Novel Nanoparticles and Engineered Nanomaterials

Date

2023-04-03

Author

Cai, Yuxin

Type of Degree

PhD Dissertation

Department

Materials Engineering

Abstract

Cancer treatment strategies such as Anti-programmed death-ligand 1 (Anti-PD-L1) or chimeric antigen receptors (CAR) T-cells are limited by low objective response rates and severe side effects. This is partly due to the lack of personalized diagnosis and treatment based on the individual immune response. This research proposes the use of a lab-on-a-chip system and point-of-care (PoC) device to provide real-time monitoring of immune response, which can help reveal the fundamental mechanisms of the disease and tailor treatment to the patient's response. The challenge lies in accessing immune status profiling and performing regulated immune therapy. To address this challenge, this research focuses on precise disease screening and developing engineering and biology techniques for immune status profiling. Localized surface plasmonic resonance (LSPR) based nanoplasmonic high throughput cytokine immunoassays and tumor-derived exosome profilings were developed to monitor cytokine levels in the tumor microenvironment. The former utilizes LSPR to monitor cytokine levels in the tumor microenvironment, while the latter identifies tumor-associated antigens that can activate immunological cell death and inhibit cancer metastasis. Additionally, this research proposes a combined immunological cancer therapy design using copper ferrite nanoparticles as a drug load. These nanoparticles can be magnetically delivered to the tumor area, providing anti-cancer ingredients and hyperthermia effects to eliminate tumor cells. The therapy generates tumor-associated antigens that activate immunological cell death and inhibit the epithelial-mesenchymal transition to prevent cancer metastasis. Besides considering increasing the objective rate of the immune response, immune status profiling also plays a vital role in moderating the side effects of some immune regulating strategies. Much about the mammalian nervous system and the brain's structures, functions, and connections remain unknown. Therefore, the microneedle biosensors for in-situ analysis of neuron signaling toward the human-computer interface were designed to provide both a neuron cytotoxic drug screening platform and a comprehensive understanding of neuron active mechanisms. Overall, this research presents a promising approach to improve cancer treatment by combining engineering and biology techniques to monitor immune responses and tailor treatment based on individual responses.