19 research outputs found
Carbon Nanotubes in Biology and Medicine: in vitro and in vivo Detection, Imaging and Drug Delivery
Carbon nanotubes exhibit many unique intrinsic physical and chemical
properties and have been intensively explored for biological and biomedical
applications. In this review, we summarize the main results of our and other
groups in this field and clarify that surface functionalization is critical to
the behaviors of carbon nanotubes in biological systems. Ultra-sensitive
detection of biological species with carbon nanotubes can be realized after
surface passivation to inhibit the non-specific binding of bio-molecules on the
hydrophobic nanotube surface. Electrical nanosensors based on nanotubes provide
a label-free approach to biological detections. Surface enhanced Raman
spectroscopy of CNT opens up a method of protein microarray with down to 1 fM
detection sensitivity. In vitro and in vivo toxicity studies reveal that well
water soluble and serum stable nanotubes are biocompatible, non-toxic and
potentially useful for biomedical applications. In vivo biodistributions vary
with the functionalization and possibly also sizes of nanotubes, with a
tendency of accumulation in the reticuloendothelial systems, including the
liver and spleen, after intravenous administration. If well functionalized,
nanotubes may be excreted mainly through the biliary pathway in feces. Carbon
nanotube-based drug delivery has shown promises in various in vitro and in vivo
experiments including delivery pf small interfering RNA, paclitaxel and
doxorubicin. Moreover, SWNTs with various interesting intrinsic optical
properties have been used as novel photoluminance, Raman and photoacoustic
contrast agents for imaging of cells and animals. Further multidisciplinary
explorations in this field are promising and may bring new opportunities to the
realm of biomedicine.Comment: To appear in Nano Research,
http://www.springerlink.com/content/m6t5871n55841736/?p=53184a51bcfd44239b9091ee7e1ef67
Multiplexed five-color molecular imaging of cancer cells and tumor tissues with carbon nanotube Raman tags in the near-infrared
Single-walled carbon nanotubes (SWNTs) with five different C13/C12 isotope
compositions and well-separated Raman peaks have been synthesized and
conjugated to five targeting ligands in order to impart molecular specificity.
Multiplexed Raman imaging of live cells has been carried out by highly specific
staining of cells with a five-color mixture of SWNTs. Ex vivo multiplexed Raman
imaging of tumor samples uncovers a surprising up-regulation of epidermal
growth factor receptor (EGFR) on LS174T colon cancer cells from cell culture to
in vivo tumor growth. This is the first time five-color multiplexed molecular
imaging has been performed in the near-infrared (NIR) region under a single
laser excitation. Near zero interfering background of imaging is achieved due
to the sharp Raman peaks unique to nanotubes over the low, smooth
autofluorescence background of biological species.Comment: Published in Nano Researc
High Performance In Vivo Near-IR (>1 {\mu}m) Imaging and Photothermal Cancer Therapy with Carbon Nanotubes
Short single-walled carbon nanotubes (SWNTs) functionalized by PEGylated
phospholipids are biologically non-toxic and long-circulating nanomaterials
with intrinsic near infrared photoluminescence (NIR PL), characteristic Raman
spectra, and strong optical absorbance in the near infrared (NIR). This work
demonstrates the first dual application of intravenously injected SWNTs as
photoluminescent agents for in vivo tumor imaging in the 1.0-1.4 {\mu}m
emission region and as NIR absorbers and heaters at 808 nm for photothermal
tumor elimination at the lowest injected dose (70 {\mu}g of SWNT/mouse,
equivalent to 3.6 mg/kg) and laser irradiation power (0.6 W/cm2) reported to
date. Ex vivo resonance Raman imaging revealed the SWNT distribution within
tumors at a high spatial resolution. Complete tumor elimination was achieved
for large numbers of photothermally treated mice without any toxic side effects
after more than six months post-treatment. Further, side-by-side experiments
were carried out to compare the performance of SWNTs and gold nanorods (AuNRs)
at an injected dose of 700 {\mu}g of AuNR/mouse (equivalent to 35 mg/kg) in NIR
photothermal ablation of tumors in vivo. Highly effective tumor elimination
with SWNTs was achieved at 10 times lower injected doses and lower irradiation
powers than for AuNRs. These results suggest there are significant benefits of
utilizing the intrinsic properties of biocompatible SWNTs for combined cancer
imaging and therapy.Comment: Nanoresearch, in pres
An integrated peptide-antigen microarray on plasmonic gold films for sensitive human antibody profiling.
High-throughput screening for interactions of peptides with a variety of antibody targets could greatly facilitate proteomic analysis for epitope mapping, enzyme profiling, drug discovery and biomarker identification. Peptide microarrays are suited for such undertaking because of their high-throughput capability. However, existing peptide microarrays lack the sensitivity needed for detecting low abundance proteins or low affinity peptide-protein interactions. This work presents a new peptide microarray platform constructed on nanostructured plasmonic gold substrates capable of metal enhanced NIR fluorescence enhancement (NIR-FE) by hundreds of folds for screening peptide-antibody interactions with ultrahigh sensitivity. Further, an integrated histone peptide and whole antigen array is developed on the same plasmonic gold chip for profiling human antibodies in the sera of systemic lupus erythematosus (SLE) patients, revealing that collectively a panel of biomarkers against unmodified and post-translationally modified histone peptides and several whole antigens allow more accurate differentiation of SLE patients from healthy individuals than profiling biomarkers against peptides or whole antigens alone
Graphite-Coated Magnetic Nanoparticle Microarray for Few-Cells Enrichment and Detection
Graphite-coated, highly magnetic FeCo core–shell nanoparticles were synthesized by a chemical vapor deposition method and solubilized in aqueous solution through a unique polymer mixture modification, which significantly improved the biocompatibility and stability of the magnetic nanoparticles (MNPs). Such functionalized MNPs were proven to be very stable in different conditions which would be significant for biological applications. Cell staining, manipulation, enrichment, and detection were developed with these MNPs. Under external magnetic manipulation, the MNP-stained cells exhibited directed motions. Moreover, MNPs were printed on substrates to modulate the magnetic field distribution on the surface. Capture and detection of sparse populations of cancer cells spiked into whole blood has been explored in a microarray fashion. Cancer cells from hundreds down to only two were able to be simply and efficiently detected from 1 mL of whole blood on the MNP microarray chips. Interestingly, the cells captured through the MNP microarray still showed viability and adhered to the MNP spots after incubation, which could be utilized for cancer cell detection, localized growth, and proliferation
Peptide-antigen microarrays on plasmonic gold substrate for profiling antibodies in serum samples of SLE patients and healthy individuals.
<p>A) Box plot of serum IgG antibody reactivity against several peptides and a whole antigen for 20 SLE patients and 20 healthy controls. Acetylated histone H2B peptides were found to be able to differentiate SLE patients and healthy controls (top box plots) together with whole H2B protein (bottom left box plot). While the H3 peptide with the 18th lysine methylated were found not capable of telling SLE patient from healthy control (bottom right box plot). B–D) Heatmaps displaying antibody reactivity to (B) histone peptides only, (C) whole antigens only, and (D) a combination of histone peptides and whole antigens that are identified capable of differentiating SLE patients and healthy controls with false discovery rate (q value) <0.001. The dashed lines are drawn to highlight the separation of SLE and healthy groups identified by using the average linkage Euclidean distance hierarchical clustering method. Color intensity of each grid in the heatmap reflected mean fluorescence intensity of corresponding peptide or antigen spot on the microarray for each SLE patient or healthy individual. In (B) and (C), several SLE patients (labeled in blue and purple color) are misplaced in the healthy group. These patients are grouped in the SLE side in (D) that profiles antibodies against both peptides and whole antigens. However, one healthy individual is mis-placed in the SLE group by this approach, reducing the specificity of this analysis.</p