Differentiating tumor heterogeneity in formalin‐fixed paraffin‐embedded (FFPE) prostate adenocarcinoma tissues using principal component analysis of matrix‐assisted laser desorption/ionization imaging mass spectral data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135165/1/rcm7776.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135165/2/rcm7776_am.pd

A Comparative Study of Hollow Copper Sulfide Nanoparticles and Hollow Gold Nanospheres on Degradability and Toxicity

Gold and copper nanoparticles have been widely investigated for photothermal therapy of cancer. However, degradability and toxicity of these nanoparticles remain concerns. Here, we compare hollow CuS nanoparticles (HCuSNPs) with hollow gold nanospheres (HAuNS) in similar particle sizes and morphology following intravenous administration to mice. The injected pegylated HCuSNPs (PEG-HCuSNPs) are eliminated through both hepatobiliary (67 percentage of injected dose, %ID) and renal (23 %ID) excretion within one month postinjection. By contrast, 3.98 %ID of Au is excreted from liver and kidney within one month after iv injection of pegylated HAuNS (PEG-HAuNS). Comparatively, PEG-HAuNS are almost nonmetabolizable, while PEG-HCuSNPs are considered biodegradable nanoparticles. PEG-HCuSNPs do not show significant toxicity by histological or blood chemistry analysis. Principal component analysis and 2-D peak distribution plots of data from matrix-assisted laser desorption ionization-time-of-flight imaging mass spectrometry (MALDI-TOF IMS) of liver tissues demonstrated a reversible change in the proteomic profile in mice receiving PEG-HCuSNPs. This is attributed to slow dissociation of Cu ion from CuS nanoparticles along with effective Cu elimination for maintaining homeostasis. Nonetheless, an irreversible change in the proteomic profile is observed in the liver from mice receiving PEG-HAuNS by analysis of MALDI-TOF IMS data, probably due to the nonmetabolizability of Au. This finding correlates with the elevated serum lactate dehydrogenase at 3 months after PEG-HAuNS injection, indicating potential long-term toxicity. The comparative results between the two types of nanoparticles will advance the development of HCuSNPs as a new class of biodegradable inorganic nanomaterials for photothermal therapy

Assessment of molecular differentiation in FFPE colon adenocarcinoma tissues using PCA analysis of MALDI IMS spectral data

MALDI IMS datasets comprise huge amounts of spectra and their interpretation requires the use of multivariate statistical methods. MALDI IMS spectral data have been processed using sequential principal component analysis and 2-D peak distribution tests so as to investigate the molecular differentiation of tumor regions in formalin-fixed paraffin-embedded tissue biopsies of colorectal adenocarcinoma. In some of the cases fresh frozen tissue section samples were also analyzed for comparison. Multivariate analysis of spectral data revealed a specific pattern of mass ion peaks in different tumor regions that were distinguishable from the adjacent normal regions within a given specimen. Moreover, similar mass ion peaks could be detected in both FFPE and fresh-frozen tissue section samples. These significant mass ion peaks have been used to generate ion images and visualize the difference between tumor and normal regions. These specific and statistically significant ion peaks may serve as potential biomarkers for colorectal adenocarcinoma

A Comparative Study of Hollow Copper Sulfide Nanoparticles and Hollow Gold Nanospheres on Degradability and Toxicity

Gold and copper nanoparticles have been widely investigated for photothermal therapy of cancer. However, degradability and toxicity of these nanoparticles remain concerns. Here, we compare hollow CuS nanoparticles (HCuSNPs) with hollow gold nanospheres (HAuNS) in similar particle sizes and morphology following intravenous administration to mice. The injected pegylated HCuSNPs (PEG-HCuSNPs) are eliminated through both hepatobiliary (67 percentage of injected dose, %ID) and renal (23 %ID) excretion within one month postinjection. By contrast, 3.98 %ID of Au is excreted from liver and kidney within one month after iv injection of pegylated HAuNS (PEG-HAuNS). Comparatively, PEG-HAuNS are almost nonmetabolizable, while PEG-HCuSNPs are considered biodegradable nanoparticles. PEG-HCuSNPs do not show significant toxicity by histological or blood chemistry analysis. Principal component analysis and 2-D peak distribution plots of data from matrix-assisted laser desorption ionization-time-of-flight imaging mass spectrometry (MALDI-TOF IMS) of liver tissues demonstrated a reversible change in the proteomic profile in mice receiving PEG-HCuSNPs. This is attributed to slow dissociation of Cu ion from CuS nanoparticles along with effective Cu elimination for maintaining homeostasis. Nonetheless, an irreversible change in the proteomic profile is observed in the liver from mice receiving PEG-HAuNS by analysis of MALDI-TOF IMS data, probably due to the nonmetabolizability of Au. This finding correlates with the elevated serum lactate dehydrogenase at 3 months after PEG-HAuNS injection, indicating potential long-term toxicity. The comparative results between the two types of nanoparticles will advance the development of HCuSNPs as a new class of biodegradable inorganic nanomaterials for photothermal therapy