Biomedical subjects

Warren C W Chan

Publications and source records attributed to Warren C W Chan.

11 recordsLinked to original sources

PubMed2006

Bionanotechnology progress and advances.

Advances in the nanotechnology research have provided a new set of research tools, materials, structures, and systems for biological and medical research and applications. These nanotechnologies include the application of fluorescent quantum dots for optical imaging, the design of metallic nanoparticle surfaces for ultrasensitive biomolecular fingerprinting, and the use of nanostructures as hyperthermia agents for cancer therapy. Unlike conventional technologies, unique properties can be incorporated into nanometer-size particles, structures, and systems simply by changing their size, shape, and composition. Because of the tunable properties, biologists and clinicians could custom-design a material for a specific research need. In this review article, we highlight the recent advances and progress in Bionanotechnology research as well as provide future perspective on this integrative field.

Biotechnology↗

PubMed2006

Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics.

We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.

Antineoplastic Agents↗

PubMed2006

Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells.

We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).

Gold↗

PubMed2006

High throughput quantification of protein expression of cancer antigens in tissue microarray using quantum dot nanocrystals.

We developed and validated a novel method for quantifying protein expression of cancer tumors in an accurate, sensitive, and high throughput format. This technique integrates quantum dots, tissue microarray, optical spectroscopy, and algorithm design for analysis of tumor biopsies. The integration of this method for tissue analysis in the clinic bears potential impact for improving the diagnosis and treatment of cancer.

Animals↗

PubMed2006

Cellular imaging and surface marker labeling of hematopoietic cells using quantum dot bioconjugates.

Semiconductor quantum dots (qdots) are emerging as a new class of fluorescent labels. The unique optical properties of qdots make them appealing in laboratory diagnosis; however, qdot-based probes remain to be developed and evaluated for clinical laboratory applications. In this study, 2 different approaches were employed to label hematopoietic cells with qdots. The first was based on a generalized intracellular delivery of qdots using qdot-transferrin conjugates through receptor-mediated endocytosis. Hematopoietic cells from umbilical cord blood or bone marrow were successfully labeled with qdot-transferrin in cell cultures. The fluorescence signal of qdot-transferrin was detected in the cytoplasmic location. The second approach was to use qdot-antibodies for labeling cell surface markers. The monoclonal antibodies to CD5, CD19, and CD45 surface antigens were conjugated to qdots with distinct emission spectra. The qdot-linked antibodies were shown to bind successfully to specific cell markers on lymphocytes. The signal obtained from the labeling of cells was detectable by using fluorescence microscopy and flow cytometry. The qdot signals were shown to be target specific, bright, and photo stable. The results of this study demonstrated the feasibility of using qdots for cell labeling and surface marker analysis of hematopoietic cells. Given the superior optical properties of qdots as compared to conventional fluorescence dyes, the qdot-based probe offers a promising tool for hematology analysis in clinical laboratories.

Antibodies, Monoclonal↗

PubMed2005

Surface-plasmon-coupled emission of quantum dots.

We studied surface plasmon-coupled emission (SPCE) of semiconductor quantum dots (QDs). These QDs are water-soluble ZnS-capped CdSe nanoparticles stabilized using lysine cross-linked mercaptoundecanoic acid. The QDs were spin-coated from 0.75% PVA solution on a glass slide covered with 50 nm of silver and a 5-nm protective SiO(2) layer. Excited QDs induced surface plasmons in a thin silver layer. Surface plasmons emitted a hollow cone of radiation into an attached hemispherical glass prism at a narrow angle of 48.5 degrees. This directional radiation (SPCE) preserves the spectral properties of QD emission and is highly p-polarized irrespective of the excitation polarization. The SPCE spectrum depends on the observation angle because of the intrinsic dispersive properties of SPCE phenomenon. The remarkable photostability can make QDs superior to organic fluorophores when long exposure to the intense excitation is needed. The nanosize QDs also introduce a roughness near the metal layer, which results in a many-fold increase of the coupling of the incident light to the surface plasmons. This scattered incident illumination transformed into directional, polarized radiation can be used simultaneously with SPCE to develop devices based on both quantum dot emission and light scattered from surface plasmons on a rough surface.

Cadmium Compounds↗

PubMed2004

Semiconductor quantum dots as contrast agents for whole animal imaging.

Recent developments in quantum dot (QD) technology have paved the way for using QDs as optical contrast agents for in vivo imaging. Pioneering papers showed the use of QDs as luminescent contrast agents for imaging cancer and guiding cancer surgery. The possible future use of QDs for clinical applications is expected to have a significant impact, however many challenges in this field have yet to be overcome.

Contrast Media↗

PubMed2002

Nanocrystal targeting in vivo.

Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter known as the reticuloendothelial system. We set out to explore the feasibility of in vivo targeting by using semiconductor quantum dots (qdots). Qdots are small (<10 nm) inorganic nanocrystals that possess unique luminescent properties; their fluorescence emission is stable and tuned by varying the particle size or composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting peptide accumulate in the lungs of mice after i.v. injection, whereas two other peptides specifically direct qdots to blood vessels or lymphatic vessels in tumors. We also show that adding polyethylene glycol to the qdot coating prevents nonselective accumulation of qdots in reticuloendothelial tissues. These results encourage the construction of more complex nanostructures with capabilities such as disease sensing and drug delivery.

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

Assessing porcine liver-derived biomatrix for hepatic tissue engineering.

Acellular, biologically derived matrices such as small intestinal submucosa have been extensively utilized to induce tissue regeneration and remodeling of connective tissue, vascular grafts, and urinary bladder; however, decellularized scaffolds have not been explored for their potential utility in hepatic tissue engineering. In the case of both extracorporeal hepatocyte-based devices and implantable hepatocyte-scaffold tissue-engineered constructs, maintenance of hepatocellular function is of prime importance. In this study, we specifically explored decellularized, porcine, liver-derived biomatrix (LBM) as a bioresorbable scaffold for primary hepatocytes. Primary rat hepatocytes were cultured on LBM and compared with well-characterized hepatocyte culture models--double-gel cultures that promote maintenance of liver-specific functions for many weeks, and adsorbed collagen monolayers that lead to the rapid decline of hepatocellular function and viability. Hepatocytes were maintained for up to 45 days on LBM and liver-specific functions such as albumin synthesis, urea production, and P-450 IA1 activity were found to be significantly improved over adsorbed collagen cultures. Our data indicate that LBM may be a favorable alternative to existing scaffolds for tissue engineering in that it is bioresorbable, can be easily manipulated, and supports long-term hepatocellular functions in vitro.

Animals↗