Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging

Abstract

Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5±8.2 and 23.3±4.1 particles/100μm2 within 10μm from the nearest source and few nanoparticles beyond 50μm, respectively. The spleen had 35.5±9.3 particles/100μm2 within 10μm with penetration also limited to 50μm. For SGN, the liver showed 31.1±4.1 particles/100μm2 within 10μm of the nearest source with penetration hindered beyond 30μm. The spleen and tumor showed uptake of 22.1±6.2 and 15.8±6.1 particles/100μm2 within 10μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09±0.14 in the liver, 0.74±0.12 in the spleen, and 0.43±0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43±0.07 in the liver, 0.30±0.06 in the spleen, and 0.20±0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in pancreatic tumors with the goal to improve nanotherapeutic efficacy.

An Interdisciplinary Computational/Experimental Approach to Evaluate Drug-Loaded Gold Nanoparticle Tumor Cytotoxicity

“…Characterization via zeta potential analysis showed that three-layer nanoparticles displayed a relatively neutral surface charge of -6 mV, while two-layer nanoparticles were more anionic at -21 mV (Table 2). The measurements were consistent with previous work [36][37][38]. Dynamic light scattering (DLS) provided further information regarding size based upon Brownian motion when in solution [56].…”

“…This assumes first-order kinetics, for which the extravasation is mainly concentration dependent. The decay α is measured from previous in vivo experiments, for which the nanoparticle concentration is estimated to have a half-life of 12 h [37]. Although nanoparticle diffusivity can be dependent on charge [53] in addition to size, for this study we calibrate the diffusivity to the combination of these properties as measured from the in vitro data [36].…”

“…It was shown that such layered gold nanoparticles exhibit improved penetration in comparison to PEGylated nanoparticles in 3D cell cultures representing avascular tissue [36], and that they are uptaken into solid tumor tissue in vivo [37]. Both two-and threelayer gold nanoparticles could be loaded with cisplatin or paclitaxel, eliciting unique drug release kinetics [38].…”

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

“…These results were also obtained in S2-VP10 orthotopic xenograft tumor and showed the predictive value of MCTS. 104 The same statement holds for growth inhibition effects measured in MCTS and in vivo tumors subjected to NPs' treatment. The similarity between the evolution of spheroid volume and tumor growth after treatment constitutes a great advantage with respect to 2D cell models.…”

Laser thermal ablation of multidrug-resistant bacteria using functionalized gold nanoparticles

“…1,[8][9][10][11] Due to their physical properties and potencies, nanoparticles have proven to be highly versatile and can be widely used in numerous applications. 6,[12][13][14] Their size and shape properties are compatible with various biomedical applications that require interaction with smallmolecule antibiotics. The size of these nanomaterials provides a large surface-areato-volume ratio, which enables the binding of a large number of high affinity ligands, allowing for nanoparticle multivalency in fighting bacteria.…”