Abstract 2800: The effect of surface protein adsorption on gold nanoparticle-intratumoral distribution and retention in a pre-clinical model of non-small cell lung cancer
Authors: Terracciano Rossana , Butler Brian E. , Demarchi Danilo , Grattoni Alessandro , Filgueira Carly S. 
Published: July 2021

Abstract
Nanomedicine's inability to penetrate throughout an entire tumor volume, resulting from heterogeneous distribution within the tumor mass, remains a crucial limiting factor for a vast range of theranostic applications. Despite innumerable studies conducted on the topic that have shown efficacy and biocompatibility of colloidal gold nanoparticles (GNPs), the biological effects of GNPs in the tumor microenvironment, including particle-protein interactions and consequent impacts on cellular pathways and contrast enhancement, remain unclear. For this reason, we aim to evaluate the influence of protein surface adsorption on GNP biodistribution in Lewis Lung Carcinoma (LLC) tumor-bearing mice using high resolution Computed Tomography (CT) preclinical imaging. We chose LLC as it is the only reproducible syngeneic model for lung cancer to date. We hypothesize that by controlling the adsorption of proteins on the GNP surface, we can influence the intratumoral distribution and retention of the particles. GNPs are synthesized, surface passivated with Bovine Serum Albumin (BSA) and characterized with standard methods. Modulation of BSA adsorption on the GNPs is observed by tuning the pH of the immobilization medium from acidic to alkaline, which we quantify using Langmuir isotherms. CT phantom imaging is used to determine X-ray attenuation as a function of GNP concentration and surface functionalization. In vitro studies evaluating the uptake of GNPs by Lewis Lung Carcinoma cells highlighted a difference in internalization depending on the surface functionalization. The in vivo study is performed by injecting concentrated GNPs intratumorally into LLC solid tumors grown on the right flank of 6-week old female C57BL/6 mice. Follow-up assessments with CT attenuation quantification based on bioimaging analysis for each time point is conducted. In vivo results show significant heterogeneity in the intratumoral biodistribution of GNPs dependent on surface passivation. CT and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) results both confirm that particles remain in the tumor 9 days post-injection (n=8 mice per group). Significant difference is highlighted between citrate-GNPs and BSA-GNPs groups (**p &lt; 0.005, Tukey's multiple comparisons test), confirming the protein corona of GNPs as a modifier factor for intratumoral distribution and retention of the particles. No significant traces of gold are found in other organs after 9 days (spleen, kidneys, liver, and lung). In conclusion, our investigations have shown that surface passivation of GNPs is able to influence the mechanism of cellular uptake in vitro and their in vivo intratumoral diffusion highlighting the spatial heterogeneity of the solid tumor.
Citation Format: Rossana Terracciano, Brian E. Butler, Danilo Demarchi, Alessandro Grattoni, Carly S. Filgueira. The effect of surface protein adsorption on gold nanoparticle-intratumoral distribution and retention in a pre-clinical model of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2800.