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. 2020 Jan 21;92(2):2011-2018.
doi: 10.1021/acs.analchem.9b04398. Epub 2019 Dec 30.

Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects

Affiliations

Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects

Kristen N Sikora et al. Anal Chem. .

Abstract

Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with anti-TNF-α siRNA cause changes to the lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-α, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, LA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-α production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MALDI-MSI and iron signals from LA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.

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Figures

Figure 1.
Figure 1.
NPSC composition and AuNP-ligand structure. Arginine-based ligands (arginine shown in red) are conjugated to the AuNPs. The Arg-AuNPs are emulsified with linoleic acid and allowed to associate with the siRNA cargo.
Figure 2.
Figure 2.
Representative images of lipid responses in NPSC-injected mouse spleen tissues (right in each image pair) compared to control tissues (left in each image pair). Panels (a) and (d) are examples of lipids predicted to increase in the spleen upon TNF-α knockdown. Panels (b) and (e) are examples of lipids predicted to decrease in the spleen upon TNF-α knockdown. Panels (c) and (f) are examples of lipids predicted to retain consistent levels upon TNF-α knockdown.
Figure 3.
Figure 3.
Example images of lipid responses in NPSC-injected mouse spleen tissues (right in each image pair) compared to control tissues (left in each image pair) with heme B overlays to determine sub-organ distribution. Heme B is indicated by red. Regions of high co-localization between the lipid and heme signals appear in yellow, whereas those with low or no co-localization appear in green. Panels (a), (b), (c), and (f) are example images of lipids that respond to the NPSCs in the white pulp of the spleen tissues, as indicated by their intense green color. In panel (f), only 22% of the control tissue lipids and 23% of the NPSC-injected lipids overlap with the heme peaks. Panels (d) and (e) are example images of lipids that respond to NPSCs in the red pulp of the spleen as indicated by their intense yellow color. In panel (d), 76% of the control tissue lipids and 85% of the NPSC-injected tissue lipids overlap with the heme peaks. In panel (e), 76% of the control tissue lipids and 71% of the NPSC-injected tissue lipids overlap with the heme peaks.
Figure 4.
Figure 4.
LA-ICP-MS images showing the distributions of iron (left) and gold (right) in a spleen tissue slice from an NPSC-injected mouse. The overlaid image (center) contains 83% co-registered (white) pixels, indicating that gold is primarily distributed in the red pulp region of the spleen where iron signals are high.
Figure 5.
Figure 5.
LA-ICP-MSI and MALDI-MSI image overlays of iron and heme B distributions to correlate the two imaging modalities. These analytes are markers for hemoglobin, which has a high concentration in the vascularized red pulp of the spleen. In the overlaid images, 70% of the signal pixels are yellow, indicating the expected high co-localization of iron and heme B in the red pulp.
Figure 6.
Figure 6.
MALDI-MSI and LA-ICP-MSI image overlays of a lipid (i.e. PC 36:0) that changes upon NPSC injection and gold from the NPSCs, illustrating that the lipid changes occur in regions low in gold. In the overlaid images, only 34% of the signal pixels are yellow, indicating relatively how colocalization between the lipid of interest and gold.

References

    1. De M; Ghosh PS; Rotello VM Applications of Nanoparticles in Biology.. Adv. Mater 2008, 20 (22), 4225–4241. 10.1002/adma.200703183. - DOI
    1. Dreaden EC; Alkilany AM; Huang X; Murphy CJ; El-Sayed M. a. The Golden Age: Gold Nanoparticles for Biomedicine. Chem. Soc. Rev 2012, 41 (7), 2740 10.1039/c1cs15237h. - DOI - PMC - PubMed
    1. Yu X; Trase I; Ren M; Duval K; Guo X; Chen Z Design of Nanoparticle-Based Carriers for Targeted Drug Delivery. J. Nanomater 2016, 2016, 1087250 10.1155/2016/1087250. - DOI - PMC - PubMed
    1. Kumar B; Jalodia K; Kumar P; Gautam HK Recent Advances in Nanoparticle-Mediated Drug Delivery. J. Drug Deliv. Sci. Technol 2017, 41 (6), 260–268. 10.1016/j.jddst.2017.07.019. - DOI
    1. Liu J; Stace-Naughton A; Jiang X; Brinker CJ Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicles. J. Am. Chem. Soc 2009,131 (4), 1354–1355. 10.1021/ja808018y. - DOI - PMC - PubMed

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