Single-walled carbon nanotubes are currently under evaluation in biomedical applications, including in vivo delivery of drugs, proteins, peptides and nucleic acids (for gene transfer or gene silencing), in vivo tumour imaging and tumour targeting of single-walled carbon nanotubes as an anti-neoplastic treatment. However, concerns about the potential toxicity of single-walled carbon nanotubes have been raised. Here we examine the acute and chronic toxicity of functionalized single-walled carbon nanotubes when injected into the bloodstream of mice. Survival, clinical and laboratory parameters reveal no evidence of toxicity over 4 months. Upon killing, careful necropsy and tissue histology show age-related changes only. Histology and Raman microscopic mapping demonstrate that functionalized single-walled carbon nanotubes persisted within liver and spleen macrophages for 4 months without apparent toxicity. Although this is a preliminary study with a small group of animals, our results encourage further confirmation studies with larger groups of animals.
This study evaluates the influence of particle size, PEGylation, and surface coating on the quantitative biodistribution of near-infrared-emitting quantum dots (QDs) in mice. Polymer- or peptide-coated 64Cu-labeled QDs 2 or 12 nm in diameter, with or without polyethylene glycol (PEG) of molecular weight 2000, are studied by serial micropositron emission tomography imaging and region-of-interest analysis, as well as transmission electron microscopy and inductively coupled plasma mass spectrometry. PEGylation and peptide coating slow QD uptake into the organs of the reticuloendothelial system (RES), liver and spleen, by a factor of 6–9 and 2–3, respectively. Small particles are in part renally excreted. Peptide-coated particles are cleared from liver faster than physical decay alone would suggest. Renal excretion of small QDs and slowing of RES clearance by PEGylation or peptide surface coating are encouraging steps toward the use of modified QDs for imaging living subjects.
An optimized noninvasive Raman microscope was used to evaluate tumor targeting and localization of single walled carbon nanotubes (SWNTs) in mice. Raman images were acquired in two groups of tumor-bearing mice. The control group received plain-SWNTs, whereas the experimental group received tumor targeting RGD-SWNTs intravenously. Raman imaging commenced over the next 72 h and revealed increased accumulation of RGD-SWNTs in tumor (p < 0.05) as opposed to plain-SWNTs. These results support the development of a new preclinical Raman imager.Raman spectroscopy is a well established bioanalytical tool with many advantages including excellent sensitivity to small structural and chemical changes, minimal sample preparation, high spatial resolution, and resistance to autofluorescence and photobleaching. 1 Although scientists have reported the use of Raman spectroscopy to image biological processes within living cells and excised tissues, 2-7 its inherently weak effect has limited its application to noninvasively assess small animal models. However, with careful system design and appropriate modifications, our laboratory has developed a Raman microscope capable of noninvasive deep tissue imaging. 8 The current paper focuses on the ability of our optimized Raman microscope to effectively localize functionalized single wall nanotubes (SWNTs) in a tumor model. Carbon nanotubes have played a fundamental role in the rapidly developing field of nanotechnology because of their unique properties and high potential in biomedical applications including targeted chemotherapeutics, diagnostic imaging contrast agents, and photoablative therapy agents. 9,10 Absence of acute toxicity, relatively long circulation time, and rapid renal clearance also make SWNTs an attractive diagnostic and therapeutic nanodevice. 9,11 Raman spectroscopy has proven to be a valuable tool for characterizing SWNTs. The inherent Raman peak, referred to as the G-band (~1593 cm −1 ), is associated with the graphite in SWNTs and makes them ideal for high sensitivity detection with our Raman microspectroscopy system. 8These quasi-one-dimensional structures (Supporting Information (SI) Figure 1) Using microPET to evaluate effective targeting, involves the use of additional labeling of radioactive material to SWNTs. Additionally, in the RGD conjugated SWNT study reported by Liu et al., animals were sacrificed at 8 hours for tissue evaluation with Raman imaging preventing longitudinal assessment of tumor targeting. Our optimized system takes advantage of the inherent Raman peak of the graphite structure in SWNTs to noninvasively image internal tissue systems (i.e., liver, tumor models) over an extended period of time in the same mouse without adding radioactive isotopes that could potentially influence experimental therapeutic outcome. In addition, the modification of SWNTs with both a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) metal chelator and an RGD peptide is difficult to prepare; and the radiolabeling procedure can be costly and ti...
This study evaluates the quantitative biodistribution of commercially available CdSe quantum dots (QD) in mice. Methods: 64 Cu-Labeled 800-or 525-nm emission wavelength QD (21-or 12-nm diameter), with or without 2,000 MW (molecular weight) polyethylene glycol (PEG), were injected intravenously into mice (5.55 MBq/25 pmol QD) and studied using well counting or by serial microPET and region-of-interest analysis. Results: Both methods show rapid uptake by the liver (27.4-38.9 %ID/ g) (%ID/g is percentage injected dose per gram tissue) and spleen (8.0-12.4 %ID/g). Size has no influence on biodistribution within the range tested here. Pegylated QD have slightly slower uptake into liver and spleen (6 vs. 2 min) and show additional low-level bone uptake (6.5-6.9 %ID/g). No evidence of clearance from these organs was observed. Conclusion: Rapid reticuloendothelial system clearance of QD will require modification of QD for optimal utility in imaging living subjects. Formal quantitative biodistribution/imaging studies will be helpful in studying many types of nanoparticles, including quantum dots. Quant um dots (QD) are fluorescent semiconductor nanocrystals with high quantum yield, resistance to photobleaching, narrow emission peak, tunable emission wavelength, and constant excitation profile regardless of emission wavelength, making them interesting for in vivo smallanimal imaging (1,2). Naturally hydrophobic, QD are made water-soluble by surface conjugation (1). Targeting molecules, such as antibodies (3), aptamers (4), peptides (5,6), folate (7), or high-molecular-weight dextran (8) can then be added. Polyethylene glycol (PEG) is commonly attached to the surface of QD for in vivo applications. Pegylation increases in vivo circulation times of nanoparticles and liposomes, likely by sterically hindering the absorption of opsonizing proteins and, thus, delaying recognition and clearance by the reticuloendothelial system (RES) (9,10).QD have been used for in vivo fluorescence imaging for fluorescence sentinel lymph node mapping (11-13), or diffusion analysis of the brain extracellular space (14), in which particle size confines QD to a specific compartment or clearance route. Other studies have used surface modifications to target QD. Akerman et al. used ex vivo fluorescence microscopy to show lung and tumor vasculature targeting of peptide-and 5,000 MW (molecular weight) PEG-coated CdSe/ZnS QD (5). Significant liver and spleen uptake of QD was noted, and it remains unclear whether tumor uptake in this study would have been sufficient for in vivo noninvasive fluorescence imaging. In vivo fluorescence imaging of targets expressed in tumor vasculature and tumor tissues has been reported by our group (a v b 3 integrin targeting using 15-to 20-nm-wide CdSe/ZnS QD coated with RGD peptide and 2,000 MW PEG (6), and others (prostate-specific membrane antigen [PSMA] targeting with 10-to 15-nm-diameter CdSe/ZnS QD coated with anti-PSMA monoclonal antibodies and 5,000 MW PEG (3)). Both reports show significant QD uptake in liver and...
Purpose:To evaluate in vivo whole-body biodistribution of microbubbles (MBs) targeted to tumor angiogenesis-related vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by using dynamic micro-positron emission tomography (PET) in living mice. Materials and Methods:Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Lipid-shell perfluorocarbon-filled MBs, targeted to VEGFR2 via anti-VEGFR2 antibodies, were radiolabeled by conjugating the radiofluorination agent N-succinimidyl-4-[ 18 F]fluorobenzoate (SFB) to the anti-VEGFR2 antibodies. These MBs were then injected intravenously into nude mice (n ϭ 4) bearing angiosarcomas, and the whole-body biodistribution of these probes was assessed for 60 minutes by using dynamic micro-PET. Results were compared with ex vivo gamma counting (n ϭ 6) and immunofluorescence staining (n ϭ 6). Control studies in angiosarcoma-bearing mice were performed with injection of the radiolabeled antibodies alone (n ϭ 3) or free SFB (n ϭ 3). A mixed-effects regression of MB accumulation on fixed effects of time and tissue type (tumor or muscle) and random effect of animal was performed. Results:VEGFR2-targeted MBs rapidly cleared from the blood circulation (50% blood clearance after approximately 3.5 minutes) and accumulated in the liver (mean, 33.4% injected dose [ID]/g Ϯ 13.7 [standard deviation] at 60 minutes) and spleen (mean, 9.3% ID/g Ϯ 6.5 at 60 minutes) on the basis of micro-PET imaging. These findings were confirmed with ex vivo gamma counting. Uptake of targeted MBs was significantly higher (P Ͻ .0001) in tumor than in adjacent skeletal muscle tissue. Immunofluorescence staining demonstrated accumulation of the targeted MBs within hepatic Kupffer cells and splenic macrophages. Biodistribution of the radiolabeled antibodies and free SFB differed from the distribution of the targeted MBs.
GRS had a higher tumour detection rate than SRS and PET in our study. GRS in combination with CT was most effective in the detection of metastatic MTC.
No abstract
Contesting recent reports, fLuc bioluminescence does not generate sufficient photons to induce Rose Bengal or hypericin photodynamic toxicity in a range of malignant and nonmalignant cell lines, and is not suitable as a generalizable approach to antineoplastic therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.