Retention Of Gold Nanoparticles Research Articles

Docetaxel-Mediated Uptake and Retention of Gold Nanoparticles in Tumor Cells and in Cancer-Associated Fibroblasts.

Simple SummaryCurrently, radiotherapy and chemotherapy are the most commonly used options, in addition to surgery, to treat cancer. There has been tremendous progress in interfacing nanotechnology to current cancer therapeutic protocols. For example, nanoparticles are used as drug carriers in chemotherapy and as radiation dose enhancers in radiotherapy. However, most of the work to date has been focused on tumor cells. To make significant progress in this field, we need to consider the tumor microenvironment, especially cancer-associated fibroblast cells that promote tumor growth. Our study shows the potential of targeting both tumor cells and cancer-associated fibroblasts to reap the full benefits of cancer nanomedicine.Due to recent advances in nanotechnology, the application of nanoparticles (NPs) in cancer therapy has become a leading area in cancer research. Despite the importance of cancer-associated fibroblasts (CAFs) in creating an optimal niche for tumor cells to grow extensively, most of the work has been focused on tumor cells. Therefore, to effectively use NPs for therapeutic purposes, it is important to elucidate the extent of NP uptake and retention in tumor cells and CAFs. Three tumor cell lines and three CAF cell lines were studied using gold NPs (GNPs) as a model NP system. We found a seven-fold increase in NP uptake in CAFs compared to tumor cells. The retention percentage of NPs was three-fold higher in tumor cells as compared to CAFs. Furthermore, NP uptake and retention were significantly enhanced using a 50 nM concentration of docetaxel (DTX). NP uptake was improved by a factor of three in tumor cells and a factor of two in CAFs, while the retention of NPs was two-fold higher in tumor cells compared to CAFs, 72 h post-treatment with DTX. However, the quantity of NPs in CAFs was still three-fold higher compared to tumor cells. Our quantitative data were supported by qualitative imaging data. We believe that targeting of NPs in the presence of DTX is a very promising approach to accumulate a higher percentage of NPs and maintain a longer retention in both tumor cells and CAFs for achieving the full therapeutic potential of cancer nanotechnology.

Abstract PO-058: Intratumoral distribution and retention of gold nanoparticles characterized by computed tomography in a non-small cell lung cancer model

Abstract Lung cancer produces the highest number of cancer-related deaths worldwide. Currently, Non-Small Cell Lung Cancer (NSCLC) accounts for more than 85% of those cases. To date, achieving an early and precise diagnosis of NSCLC remains challenging due to extensive intratumor heterogeneity, which concerns not only to tumor epithelial cells but also the diverse microenvironment with which the tumor cells interact. In addition, genetic and phenotypic tumor heterogeneity and consequent non-uniform spatial drug distribution can lead to therapy resistance in cancer treatment. Therefore, visualization of the tumor microenvironment using morphological imaging techniques such as computed tomography (CT) can better clarify structure, vasculature, and biodistribution, making possible optimization of applications in the fields of diagnostics as well as individualized treatment. In this study, we aim to evaluate the intratumoral distribution of Gold Nanoparticles (GNPs) in Lewis Lung Carcinoma (LLC) tumor-bearing mice using high resolution CT preclinical imaging. We hypothesize that by exploiting the adsorption of molecules on the GNP surface, we can influence the intratumoral distribution and retention of the particles. In fact, GNPs exhibit high X-Ray attenuation and optimal biocompatibility, compared to the common side effects associated with the administration of standard contrast agents. GNPs approximately 34 nm in diameter are synthesized and surface passivated with Bovine Serum Albumin (BSA) to reduce opsonization and improve colloidal stability. CT phantom imaging is used to determine X-ray attenuation as a function of GNP concentration and surface functionalization. Particle uptake in vitro within the LLC cells was dependent on surface passivation. An in vivo study is performed by injecting intratumorally, concentrated GNPs into LLC-solid tumors grown on the right flank of 6-week old female C57BL/6 mice. Ten days post-injection, follow-up assessments with CT imaging and quantifications show the intratumoral distribution and retention of the particles. In vivo results show significant heterogeneity in the intratumoral biodistribution of GNPs dependent on surface passivation. BSA-GNPs perfuse predominately along the tumor periphery, allowing the visualization of the tumor boundaries, with few depositions throughout the entire tumor volume over time. This response suggests perfusion rather than permeability as the limiting factor for tumor accumulation of the GNPs. Citation Format: Rossana Terracciano, Sara Ricchetti, E. Brian Butler, Danilo Demarchi, Alessandro Grattoni, Carly S. Filgueira. Intratumoral distribution and retention of gold nanoparticles characterized by computed tomography in a non-small cell lung cancer model [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-058.

Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy.

One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to a synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. We used HeLa and MDA-MB-231 cells for our study. Cells were incubated with GNPs (0.2 nM) in the absence and presence of DTX (50 nM) for 24 h to determine uptake, distribution, and retention of NPs. For RT experiments, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a decrease in cell survival and increase in DNA damage with the triple combination of RT/ GNPs/DTX vs RT/DTX. Our experimental therapeutic results were supported by Monte Carlo simulations. The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization.

Effect of cationic polyacrylamides on the aggregation and SERS performance of gold nanoparticles-treated paper

This study examines and quantifies the effect of cationic polyelectrolyte adsorption on paper on the aggregation and retention of gold nanoparticles (AuNPs) to optimize their Surface Enhanced Raman Scattering (SERS) enhancement factor and sensitivity. Aggregation of metallic nanoparticles is known as a key factor for intense SERS enhancement. Paper substrates were treated with aqueous solutions of cationic polyacrylamide (CPAM) varying in concentration, charge density, and molecular weight to control the AuNPs’ aggregate size distribution and surface coverage on paper. The Raman Enhancement Factor of AuNPs-CPAM paper was almost an order of magnitude greater than for the untreated AuNPs paper. The high loading and uniform distribution of AuNPs aggregates on CPAM pre-treated paper contributed toward the excellent SERS reproducibility, sensitivity, and high enhancement factor. This configuration of AuNP on paper was favoured by treating the substrate with CPAM solutions of higher concentrations, higher charge density, and greater molecular weight.

Retention of gold nanoparticles in the structure of quasinematic layers formed by DNA molecules

Gold nanoparticles are shown to get incorporated into double-stranded DNA molecules forming quasinematic layers in the cholesteric liquid-crystalline dispersion particles. The process of nanoparticle incorporation results in distortion in an ordered arrangement of the neighboring dsDNA molecules in a layer and in global spatial structure of particles of the dispersion, which may be one of the possible causes of the genotoxicity of gold nanoparticles.