Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, an implantable miniaturized device has been developed using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Named Implantable Miniature Optical Fiber Device (IMOD), this device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering IMOD as outstandingly valuable for on-demand delivery of potent immunotherapeutics without exacerbating toxicities. Rigorous studies performed using IMOD are presented and discussed in the follow chapters, followed by exploration of proposed work to expand the breadth of functions offered by this implantable biomedical platform. / Doctor of Philosophy / Aside from efficient energy and data transfer, optical fibers today are used in varying fields including optogenetics and neuroscience. However, merging fiber optics with therapeutics against cancer has rarely been reported. We establish a versatile polymer/drug integrated optical fiber for both diagnosis and treatment of cancers, with minimum mechanical invasiveness. Release profiles of polymer/drug nanoparticles loaded onto our fibers, regardless of their hydrophilicity, can be adjusted to accommodate both short-term and long-term delivery specifications. This enhances intratumoral drug accumulation with minimal systemic toxicity, thus overcoming the dosing obstacle. The optical fibers are also ideal to be utilized during photodynamic therapy (PDT), since photosensitizers can be easily incorporated and activated by near-infrared light traveling through the fibers. Hollow channel within the optical fiber allows for repetitive on-demand delivery of immune checkpoint inhibitors to surrounding tumor tissue, thus stimulating and reactivating cytotoxic and helper T cells. The synergistic combination of PDT and immunotherapy can potentially boost the tumor-targeted treatment outcome by numerous folds. Lastly, our optical fibers are adaptable to integrate biosensing functionality. Devices are built upon the optical fibers to monitor treatment outcome along tumor regression. Our data establishes a correlation between tumor impedance and tumor volumes, thus allowing us to track tumor progression and treatment response towards administered treatments.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/106790 |
| Date | 30 November 2021 |
| Creators | Chin, Ai Lin |
| Contributors | Chemical Engineering, Tong, Rong, Jia, Xiaoting, Lu, Chang, Goldstein, Aaron S. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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