Date of Award

2025-08-01

Degree Name

Master of Science

Department

Biomedical Engineering

Advisor(s)

Wilson Poon

Abstract

Hepatocellular carcinoma (HCC) is currently ranked as the second leading cause of cancer-related mortality worldwide, causing more than 700,000 deaths a year. The liver is important in blood filtration and metabolism, and for this reason is a prime target for drug delivery, with lipid nanoparticles (LNPs) showing promise as carriers due to their natural hepatic tropism. However, LNP efficacy is decreased in HCC due to the limited understanding of liver physiology in cancerous environments. This project proposes to address this gap by using a tissue-clearing technique known as CLARITY along with a chemically tagged LNP for comprehensive visualization of LNPs in the liver using 3D optical microscopy. CLARITY allows whole-organ 3D fluorescent imaging, offering a better perspective into LNPs' interaction with cellular and non-cellular components. First, we aim to optimize the chemical tags on the LNPs to make them compatible with the CLARITY tissue-clearing technique. Next, we apply our chemically tagged LNPs to quantify LNP accumulation in altered physiological states, including fibrosis, cirrhosis, and HCC. This project successfully quantified collagen content across different lobes of fibrotic and healthy livers, demonstrating fibrosis development through segmentation analysis. It also validated the effective tracking of LNP accumulation in the liver at 1, 24, and 72 hours post-injection, while preserving ECM proteins, fluorescent signals, blood network, and the intact LNP chemical tag. These findings offer insight into physiological changes in fibrotic liver tissue and present a platform for studying LNP localization and therapeutic efficacy in other organs.

Language

en

Provenance

Received from ProQuest

File Size

50 p.

File Format

application/pdf

Rights Holder

Mario Yomir Mata Corral

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