1. Exploring Tissue Penetration Behaviors of Nanoparticles for Cancer Therapy
- Author
-
Chen, Wenjing
- Abstract
Cancer is a leading cause of death globally, and established therapeutic options have limits. Nanoparticles, which are distinguished by their versatility in size, shape, and surface charge, have shown great promise in tumor diagnostics and therapy. Nanoparticles increase therapeutic efficacy while decreasing toxicity by delivering drugs to target tumors. While multiple studies have revealed nanoparticles' great potential as anticancer drug carriers, their therapeutic efficiency remains limited, partly due to the poor understanding of the penetration behavior of nanoparticles within tumors. Understanding the nanoparticle penetration behavior and the factors that control this process is crucial for improving the in vivo delivery efficiency of nanoparticles. The 2D cell culture models are unable to simulate the complexities of the tumor microenvironment accurately, such as the cell-to-cell interactions and the structure of the extracellular matrix (ECM). To address these drawbacks, the 3D multicellular spheroid model was created providing an inexpensive, labor-saving, and time-saving substitute for 2D and animal models. This thesis begins by describing the penetration of tumor tissues and provides an overview of the critical factors influencing penetration into tumor tissues, including tumor-specific features and nanoparticle properties. Chapter 3 introduces a new label- free quantitative analytical technique that combines two-photon microscopy, synchrotron X-ray fluorescence microscopy (XFM), and inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution and penetration pathways of gold nanoparticles (AuNPs) of different sizes inside a tumor cell spheroid model. In Chapter 4, a hybrid approach is adopted, integrating computational and experimental techniques to create new 3D microscale Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) models. This model accurately replicates nanoparticle penetration in the extracellular tumor environment, making it a cost-effective and powerful tool for forecasting nanoparticle absorption in tumor spheroids and designing nanomedicines.
- Published
- 2024