Rapid determination of plasmonic nanoparticle agglomeration status in blood

Abstract

Plasmonic nanomaterials as drug delivery or bio-imaging agents are typically introduced to biological systems through intravenous administration. However, the potential for agglomeration of nanoparticles in biological systems could dramatically affect their pharmacokinetic profile and toxic potential. Development of rapid screening methods to evaluate agglomeration is urgently needed to monitor the physical nature of nanoparticles as they are introduced into blood. Here, we establish novel methods using darkfield microscopy with hyperspectral detection (hsDFM), single particle inductively-coupled plasma mass spectrometry (spICP-MS), and confocal Raman microscopy (cRM) to discriminate gold nanoparticles (AuNPs) and their agglomerates in blood. Rich information about nanoparticle agglomeration in situ is provided by hsDFM monitoring of the plasmon resonance of primary nanoparticles and their agglomerates in whole blood; cRM is an effective complement to hsDFM to detect AuNP agglomerates in minimally manipulated samples. The AuNPs and the particle agglomerates were further distinguished in blood for the first time by quantification of particle mass using spICP-MS with excellent sensitivity and specificity. Furthermore, the agglomeration status of synthesized and commercial NPs incubated in blood was successfully assessed using the developed methods. Together, these complementary methods enable rapid determination of the agglomeration status of plasmonic nanomaterials in biological systems, specifically blood.

Understanding the interactions between porphyrin-containing photosensitizers and polymer-coated nanoparticles in model biological environments

“…4A). 39 Fluorescence gradually recovered over 32 h when incubated in 4 wt % BSA (~600 μM, 37 °C, pH = 7.4). 40 As a control, AuNC-HPPH was also incubated in PBS, and release was monitored using supernatant absorbance at various times compared to the maximum.…”

Plasmonic nanoparticles and their characterization in physiological fluids

“…Although UV-Vis can readily distinguish primary NPs from agglomerated plasmonic NPs, the signal can be compromised by the extremely high optical density and opacity of some physiological fluids, e.g. blood [81] (Fig. 4).…”

“…However, as soon as NP-protein complexation occurs, this approach should not be followed, as the 'reference scattering' from the protein alone is not valid anymore. In this regard depolarized scattering provides a promising alternative to characterize NP in physiological fluids, which relies on the optical anisotropy of even spherical plasmonic NPs [79], which either stems from shape and/or from internal [62] Au NPs (citrate coated) PBS and BSA solutions Synthesis of advanced NPs to prevent aggregation Garcia (2015) [95] Au nanorods and spheres (glycan and PEG-coated) 10% FBS in PBS and DMEM Stability and targeting in protein rich media Pyshnaya (2014) [75] Au nanorods and spheres (PEI and BSA coated) DMEM containing 10% FBS Impact of physiological fluids on size and stability McCuspie (2011) [96] Ag NPs (BSA coated) Synthetic lung fluid Dispersion stabilization of NPs and effect on colloidal stability Jenkins (2015) [81] Au NPs (citrate coated) Blood Monitoring LSPR for aggregation studies Kah (2014) [97] Au nanorods (amphi-philic ligands coating) anisotropy. It has been shown that, compared to plasmonic NPs, scattering of depolarized light from the physiological fluid is weak, and thus, excellent 'contrast' with an essentially zero background can be obtained [58].…”

“…The ions of the element of interest are subsequently counted with a very high frequency, similar to the time scale of a particle event [118]. Particle aggregation can also be detected by monitoring the increase in signal intensity [81]. By collecting a large number of data points, particle size distributions can also be determined [119].…”

Detection, characterization and quantification of inorganic engineered nanomaterials: A review of techniques and methodological approaches for the analysis of complex samples

“…SP-ICP-MS has been used with screening purposes to detect the release of nanoparticles from plastic food containers [122,123], as well as the presence of nanoparticles and/or dissolved forms in dietary supplements [92], waste waters [4,124,125], foods and biological tissues [41] and blood [126]. SP-ICP-MS in combination with alkaline or enzymatic digestions has proven to provide reliable information about size distributions and number concentrations in laboratory studies involving food matrices spiked with silver or gold nanoparticles [32, 38, 40, 41], in tissues from organisms exposed to nanoparticles [33,37,42,124], and native nanoparticles in foods and consumer products [95].…”