Title: Interaction of Nanomaterials with Mesenchymal Stem Cells and
Development of Multifunctional Nanoparticles Targeting Cancer Stem Cells
Abstract:
One of our research focuses is on the understanding of the molecular mechanisms
underlying the interactions between nanomaterials and biological systems, and the
development of nanotechnology-based applications for diagnosis and treatment of
diseases. The first part of the talk will focus on mesenchymal stem cells (MSCs),
which are considered the cell type of choice for tissue engineering due to their
capability of multilineage differentiation. I will present our studies on the effects of
gold nanoparticles, carbon nanotubes, and silicon nanowires on the proliferation and
differentiation of MSCs and the associated molecular mechanisms involved in
osteogenesis and chandrogenesis of MSCs in the presence of nanomaterials.
Specifically, our results showed that the mechanical stimulation of SiNW arrays on
MSCs caused cytoskeleton reorganization and led to the activation of TGF-β, integrin,
and insulin signaling pathways and Ca2+ channel, which converged to stimulate the
osteogenic and chondrogenic differentiation via the Ras-Raf-mitogen-activated
protein kinase (MEK)-extracellular signal-regulated kinase (ERK) cascade. The
second part of the talk will focus on cancer stem cells (CSCs), which consist of only a
small subset of cells within a hierarchical organization of cells in tumors that is
responsible for sustaining tumorigenesis. The CSC model also provides an
explanation for resistance to both radiation and chemotherapy and eventual tumor
relapse. I will present our studies on the establishment and characterization of a CSC
model based on non-small cell lung cancer, and the development of multifunctional
nanoparticles integrating specific antibodies for targeting, fluorescence agents for
imaging, magnetic components for thermal therapy, and chemical agents for
interrupting specific pathways in the CSCs.
香港城市大学生物及化学系杨梦甦讲座教授
Professor Mengsu (Michael) Yang
Chair Professor, Department of Biology and Chemistry,
Director, Biotech and Health Centre,
City University of Hong Kong
(bhmyang@cityu.edu.hk)
Prof. Yang obtained his BSc from Xiamen University, Ph.D. from University of Toronto,
and postdoctoral training in the Scripps Research Institute in USA. He is currently Chair
Professor of Department of Biology and Chemistry and Director of the Biotech and Health
Centre of City University of Hong Kong. The research interest of Yang’s group focuses on
the development of biochip technology and nanotechnology for molecular diagnostics and
therapeutic applications. Prof. Yang has published over 270 papers in peer-reviewed
journals and 43 patents/patent applications, and delivered more than 80 invited lectures. He
holds honorary professorships in Zhejiang University, Third Military Medical University,
and University of Central Lancashire. He has been awarded the Chunhui Scholar Award by
the Ministry of Education in China in 2003, the K. C. Wong Foundation Outstanding Scholar
Award in 2004, the Shenzhen Science and Technology Innovation Award in 2006, and the
Hong Kong Technological Achievement Grand Award in 2007. He is co-founder of
Multigene Diagnostics Limited and Genetel Pharmaceuticals Limited, City University
spin-off companies specializing in developing molecular diagnostic products and
therapeutic products for early detection and treatment of diseases.
Selected publications in past five years:
Nanobiotechnology
1.
“DNA-directed self-assembly of gold nanoparticles into binary and ternary nanostructures”,
Nanotechnology, 2007, 18, 015102.
2.
“Biofunctional organic nanocrystals for quantitative detection of pathogen deoxyribonucleic Acid”,
Analytica Chimica Acta, 2007, 584, 7-11.
3.
“Interactions between carbon nanotubes and DNA polymerase and restriction endonucleases”,
Nanotechnology, 2007, 18, 025102.
4.
“Effect of silicon nanowires on HepG2 adhesion and spreading”, ChemoBioChem, 2007, 8, 1115-1118.
5.
“Inhibition of biochemical reactions by silicon nanowires through modulating enzyme activities”,
ChemoBioChem, 2007, 8, 1225-1229.
6.
“The effects of carbon nanotubes on the proliferation and differentiation of primary osteoblasts”,
Nanotechnology, 2007, 18, pp475102.
7.
“A surface-enhanced Raman spectroscopy substrate for highly sensitive label-free immunoassay”,
Applied Physics Letters, 2008, 92, pp043116.
8.
“The structure and function of ribonuclease A upon interacting with carbon nanotubes”, Nanotechnology,
2008, 19 (9), 095102.
9.
“Cell adhesion and spreading behavior on vertically aligned silicon nanowire arrays”, ACS Applied
Material Interfaces, 2009, 1(1), 30-34.
10.
“Patterned growth of vertically aligned silicon nanowire arrays for label-free DNA detection using
surface-enhanced Raman spectroscopy”, Analytical and Bioanalytical Chemistry, 2010, 397, 3143-3150.
11.
“Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells”, ACS Nano, 2010, 4,
6439-6448.
12.
“Inhibition of proliferation and differentiation of mesenchymal stem cells by carboxylated carbon
nanotubes”, ACS Nano, 2010, 4 (4), 2185–2195
13.
“Peptide-bridged assembly of hybrid nanomaterial and its application for caspase-3 detection”,
ACS Applied Materials & Interfaces, 2013, in press.
Microfluidics and Biosensors
1. “Generation of linear and non-linear concentration gradients along microfluidic channel by microtunnel
controlled stepwise addition of sample solution”, Lab on a Chip, 2007, 7, 1371 – 1373.
2. “3-D streamline steering by nodes arrayed in an entangled microfluidic network”, Lab on a Chip, 2007, 7,
1712–1716.
3. “Microfluidic formation of single cell array for parallel analysis of CRAC channel activation and
inhibition”, Analytical Biochemistry, 2010, 396, 173-179.
4. “A microfluidic device with microbead array for sensitive virus DNA detection and genotyping using
quantum dots as fluorescence labels”, Biosensors & Bioelectronics, 2010, 25, 2402-2407.
5. “Real-time monitoring of cell-cell communications evoked by mechanical stimulation of suspension cells
using an integrated microfluidics chip”, Lab on a Chip, 2010, 10, 2271-2278.
6. “Multienzyme-nanoparticles amplification for sensitive virus genotyping in microfluidics using Au
nanoparticle probes and quantum dots as labels”, Biosensors and Bioelectronics, 2011, 29, 89-96.
7. "Integrated sieving microstructures on microchannels for biological cell trapping and droplet formation",
Lab on a Chip, 2011, 11, 3352-3355.
8. “Screen printing of solder resist as master substrates for fabrication of multi-level microfluidic channels and
microstructures for cell-based applications”, Biosensors and Bioelectronics, 2013, 41, 675-683.
9. “Microfluidics study of intracellular calcium response to mechanical stimulation on single suspension cells”,
Lab on a Chip, 2013, 13, 1060-1069.
10. "Detection of cancer biomarkers using PZT ceramic resonator as the transducer of piezoelectric biosensor",
Biosensors and Bioelectronics, 2013, 46, 155-161.
Chemical Biology
1. “Hypoxia induces the activation of human hepatic stellate cells LX-2 activation through TGF- signaling
pathway”, FEBS Letters, 2007, 581, 203-210.
2. “Reversal of multidrug resistance in cancer cells”, Phytomedicine, 2007, 14, 160-165.
3. “Biphasic NF-B responses during HL-60 leukemia cell differentiation through PI3K/Akt-dependent
phosphorylation/ degradation of IB”, Experimental Cell Research, 2007, 313, 1722-1734.
4. “Magnolol suppresses NF-kB activation and NF-kB regulated gene expression through inhibition of
IkappaB kinase activation”, Molecular Immunology, 2007, 44(10), 2647-2658.
5. “Deep proteome profiling of sera from never-smoked lung cancer patients”, Biomedicine &
Pharmacotherapy, 2007, 61, 570 - 577.
6. “1p31, 7q21 and 18q21 chromosomal aberrations and candidate genes in acquired vinblastine resistance of
human cervical carcinoma KB cells”, Oncology Reports, 2008, 19 (5), 1155-1164.
7. “Effects of total favonoids and favonol glycosides from Epimedium koreanum Nakai on the proliferation
and differentiation of primary osteoblasts”, Phytomedicine, 2008, 15, 55-61.
8. “COOH-terminal truncated HBV X protein plays key role in hepatocarcinogenesis”, Clinical Cancer
Research, 2008, 14 (16), 5061-5068.
9. “Proteomic and transcriptomic study on the action of a cytotoxic saponin: Induction of endoplasmic
reticulum stress and mitochondria-mediated apoptotic pathways”, Proteomics, 2008, 8 (15), 3105-3117.
10. “Gene expression analysis of human promyelocytic leukemia HL-60 cell differentiation and cytotoxicity
induced by natural and synthetic retinoids”, Life Sciences, 2009, 84(17-18), 576-583.
11. “Transcriptional analysis of doxorubicin-induced cytotoxicityand resistance in human hepatocellular
carcinoma cell lines”, Liver International, 2009, 1338-1347.
12. “Beta-adrenergic receptors are involved in osteogenesis of mouse mesenchymal stem cells via cAMP/PKA
signaling”, Archives of Biochemistry and Biophysics, 2010, 496 (2), 77-83.
13. “Beta-adrenergic signals regulate adipogenesis of mouse mesenchymal stem cells via cAMP/PKA pathway”,
Molecular and Cellular Endocrinology, 2010, 323 (2), 201-207.
14. “Herbal formula Astragali Radix and Rehmanniae Radix exerted wound healing effect on human skin
fibroblast cell line Hs27 via the activation of transformation growth factor (TGF-) pathway and promoting
extracellular matrix (ECM) deposition”, Phytomedicine, 2012, 20, 9-16.