Biomedical subjects

Xiaohu Gao

Publications and source records attributed to Xiaohu Gao.

11 recordsLinked to original sources

PubMed2006

Emerging use of nanoparticles in diagnosis and treatment of breast cancer.

The biological application of nanoparticles is a rapidly developing area of nanotechnology that raises new possibilities in the diagnosis and treatment of human cancers. In cancer diagnostics, fluorescent nanoparticles can be used for multiplex simultaneous profiling of tumour biomarkers and for detection of multiple genes and matrix RNA with fluorescent in-situ hybridisation. In breast cancer, three crucial biomarkers can be detected and accurately quantified in single tumour sections by use of nanoparticles conjugated to antibodies. In the near future, the use of conjugated nanoparticles will allow at least ten cancer-related proteins to be detected on tiny tumour sections, providing a new method of analysing the proteome of an individual tumour. Supermagnetic nanoparticles have exciting possibilities as contrast agents for cancer detection in vivo, and for monitoring the response to treatment. Several chemotherapy agents are available as nanoparticle formulations, and have at least equivalent efficacy and fewer toxic effects compared with conventional formulations. Ultimately, the use of nanoparticles will allow simultaneous tumour targeting and drug delivery in a unique manner. In this review, we give an overview of the use of clinically applicable nanoparticles in oncology, with particular focus on the diagnosis and treatment of breast cancer.

Animals↗

PubMed2006

Multicolor quantum dots for molecular diagnostics of cancer.

In the pursuit of sensitive and quantitative methods to detect and diagnose cancer, nanotechnology has been identified as a field of great promise. Semiconductor quantum dots are nanoparticles with intense, stable fluorescence, and could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. With the emergence of gene and protein profiling and microarray technology, high-throughput screening of biomarkers has generated databases of genomic and expression data for certain cancer types, and has identified new cancer-specific markers. Quantum dots have the potential to expand this in vitro analysis, and extend it to cellular, tissue and whole-body multiplexed cancer biomarker imaging.

Animals↗

PubMed2005

Quantitative 3D fluorescence technique for the analysis of en face preparations of arterial walls using quantum dot nanocrystals and two-photon excitation laser scanning microscopy.

Traditional imaging with one-photon confocal microscopy and organic fluorophores poses several challenges for the visualization of vascular tissue, including autofluorescence, fluorophore crosstalk, and photobleaching. We studied human coronary arteries (HCAs) and mouse aortas with a modified immunohistochemical (IHC) "en face" method using quantum dot (Qdot) bioconjugates and two-photon excitation laser scanning microscopy (TPELSM). We demonstrated the feasibility of multilabeling intimal structures by exciting multicolored Qdots with only one laser wavelength (750 nm). Detailed cell structures, such as the granular appearance of von Willebrand factor (VWF) and the subcellular distribution of endothelial nitric oxide synthase, were visualized using green dots (525 nm), even when the emission maximum of these Qdots overlapped that of tissue autofluorescence (510-520 nm). In addition, sensitive fluorescence quantification of vascular cell adhesion molecule 1 expression at areas of varying hemodynamics (intercostal branches vs. nonbranching areas) was performed in normal C57Bl/6 mice. Finally, we took advantage of the photostability of Qdots and the inherent three-dimensional (3D) resolution of TPELSM to obtain large z-stack series without photobleaching. This innovative en face method allowed simple multicolor profiling, highly sensitive fluorescence quantitation, and 3D visualization of the vascular endothelium with excellent spatial resolution. This is a promising technique to define the spatial and temporal interactions of endothelial inflammatory markers and quantify the effects of different interventions on the endothelium.

Animals↗

PubMed2005

In vivo molecular and cellular imaging with quantum dots.

Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are emerging as a new class of fluorescent probe for in vivo biomolecular and cellular imaging. In comparison with organic dyes and fluorescent proteins, QDs have unique optical and electronic properties: size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. Recent advances have led to the development of multifunctional nanoparticle probes that are very bright and stable under complex in vivo conditions. A new structural design involves encapsulating luminescent QDs with amphiphilic block copolymers and linking the polymer coating to tumor-targeting ligands and drug delivery functionalities. Polymer-encapsulated QDs are essentially nontoxic to cells and animals, but their long-term in vivo toxicity and degradation need more careful study. Bioconjugated QDs have raised new possibilities for ultrasensitive and multiplexed imaging of molecular targets in living cells, animal models and possibly in humans.

Animals↗

PubMed2005

Quantum dot-encoded beads.

Multicolor optical coding for biological assays has been achieved by embedding semiconductor quantum dots into mesoporous and macroporous beads at precisely controlled ratios. Owing to their novel optical properties such as size-tunable emission and simultaneous excitation, quantum dots are ideal fluorophores for wavelength-and-intensity multiplexing. Kinetics study reveals that quantum dot doping of porous silica and polystyrene beads can be completed from seconds to minutes. The use of 10 intensity levels and six colors could theoretically code 1 million nucleic acid or protein sequences. Imaging and spectroscopic measurements indicate that the quantum dot-tagged beads are highly uniform and reproducible, yielding bead identification accuracies as high as 99.99% under favorable conditions. DNA hybridization studies demonstrate that the coding and target signals can be simultaneously read at the single-bead level. This spectral coding technology is expected to open new opportunities in gene expression studies, high-throughput screening, and medical diagnostics.

Animals↗

PubMed2004

In vivo cancer targeting and imaging with semiconductor quantum dots.

We describe the development of multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) for cancer targeting and imaging in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer and linking this amphiphilic polymer to tumor-targeting ligands and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mice indicate that the QD probes accumulate at tumors both by the enhanced permeability and retention of tumor sites and by antibody binding to cancer-specific cell surface biomarkers. Using both subcutaneous injection of QD-tagged cancer cells and systemic injection of multifunctional QD probes, we have achieved sensitive and multicolor fluorescence imaging of cancer cells under in vivo conditions. We have also integrated a whole-body macro-illumination system with wavelength-resolved spectral imaging for efficient background removal and precise delineation of weak spectral signatures. These results raise new possibilities for ultrasensitive and multiplexed imaging of molecular targets in vivo.

Animals↗

PubMed2004

Quantum dot-encoded mesoporous beads with high brightness and uniformity: rapid readout using flow cytometry.

A new generation of optically encoded beads has been prepared by using mesoporous polystyrene beads and surfactant-coated semiconductor quantum dots. In comparison with nonporous beads of similar sizes and chemical compositions, the encoded porous beads are approximately 1000 times brighter and 5 times more uniform in fluorescence intensities. Using both absolute intensity and ratiometric fluorescence coding, we show that the beads can be identified with a standard flow cytometer at 1000 beads/s. This result indicates that the multiple excited-state lifetimes and relaxation pathways of quantum dots do not limit their applications in high-speed optical detection and imaging.

Biotechnology↗

PubMed2003

Molecular profiling of single cells and tissue specimens with quantum dots.

Quantum dots are tiny light-emitting particles on the nanometer scale. They are emerging as a new class of biological label with properties and applications that are not available with traditional organic dyes and fluorescent proteins. Recent advances, as reported in Science and Nature Biotechnology, have led to quantum dot bioconjugates that are highly luminescent and stable. These bioconjugates raise new possibilities for studying genes, proteins and drug targets in single cells, tissue specimens and even in living animals.

Animals↗

PubMed2002

Luminescent quantum dots for multiplexed biological detection and imaging.

Recent advances in nanomaterials have produced a new class of fluorescent labels by conjugating semiconductor quantum dots with biorecognition molecules. These nanometer-sized conjugates are water-soluble and biocompatible, and provide important advantages over organic dyes and lanthanide probes. In particular, the emission wavelength of quantum-dot nanocrystals can be continuously tuned by changing the particle size, and a single light source can be used for simultaneous excitation of all different-sized dots. High-quality dots are also highly stable against photobleaching and have narrow, symmetric emission spectra. These novel optical properties render quantum dots ideal fluorophores for ultrasensitive, multicolor, and multiplexing applications in molecular biotechnology and bioengineering.

Biological Assay↗

PubMed2002

Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding.

Semiconductor nanoparticles in the size range of 2-6 nm are of great current interest, not only because of their size-tunable properties but also because of their dimensional similarity with biological macromolecules (e.g., nucleic acids and proteins). This similarity could allow an integration of nanomaterials with biological molecules, which would have applications in medical diagnostics, targeted therapeutics, and high-throughput drug screening. Here we report new developments in preparing highly luminescent and biocompatible CdSe quantum dots (QDs), and in synthesizing QD-encoded micro- and nano-beads in the size range of 100 nm-10 microm. We show that the optical properties of ZnS-capped CdSe quantum dots are sensitive to environmental factors such as pH and divalent cations, leading to the potential use of quantum dots in molecular sensing. We also show that chemically modified proteins can be used to coat the surface of water-soluble QDs, to restore their fluorescence, and to provide functional groups for bioconjugation. For multiplexed optical encoding, we have prepared large microbeads with sizes similar to that of mammalian cells, and small nanobeads with sizes similar to that of viruses.

Biotechnology↗

PubMedDate not supplied

Quantum dot nanocrystals for in vivo molecular and cellular imaging.

Semiconductor quantum dots (QD) are nanometer-sized crystals with unique photochemical and photophysical properties that are not available from either isolated molecules or bulk solids. In comparison with organic dyes and fluorescent proteins, QD are emerging as a new class of fluorescent labels with improved brightness, resistance against photobleaching and multicolor fluorescence emission. These properties could improve the sensitivity of biological detection and imaging by at least 10- to 100-fold. Further development in high-quality near-infrared-emitting QD should allow ultrasensitive and multicolor imaging of molecular targets in deep tissue and living animals. Here, we discuss recent developments in QD synthesis and bioconjugation, applications in molecular and cellular imaging as well as promising directions for future research.

Animals↗