Date on Master's Thesis/Doctoral Dissertation


Document Type

Master's Thesis

Degree Name



Pharmacology and Toxicology

Committee Chair

Frieboes, Hermann Bueno

Author's Keywords

Nanoparticle; 3D cell cultures; Drug delivery; Lipid nanoparticles; Drug penetration; Nanotherapy


Nanoparticles--Therapeutic use; Drug delivery devices


Nanoparticle-based systems can alleviate systemic toxicity via surface functionalization to promote tissue-specific targeting as well as passive targeting abilities [1], such as the enhanced permeation and retention effect (EPR) [2]. The transport of nanoparticles is limited in hypoxic tumor regions due to the typically impaired tumor vasculature. To enhance diffusion of nanotherapeutics within tumor tissue; functionalized citrate gold nanoparticles and silica gold nanoshells with surface modifications of phosphatidylcholine (PC) and high density lipoprotein (HDL) were synthesized. 3D cell cultures were used as a representative model of portions of hypoxic tissue in liver, lung, and pancreatic solid tumors. Our results indicate that two layered silica gold nanoshells (surface modifications of -thiol and PC) permit enhanced accumulate compared to PEGylated nanoparticles. The addition of HDL for the smaller, citrate gold nanoparticles as a third external layer provided enriched accumulation compared to PEGylated nanoparticles. In conclusion, nanoparticles functionalized with PC and HDL show superior accumulation in avascular tumor tissue in comparison to previously designed PEGylated nanoparticles.