Wolfgang J Parak, Daniele Gerion, Teresa Pellegrino, Daniela Zanchet, Christine Micheel,

Shara C Williams, Rosanne Boudreau, (2002)“Biological applications of

colloidal nanocrystals” Due to their interesting properties, research on

colloidal nanocrystals has moved in the last few years from fundamental

research to first applications in materials science and life sciences. In this

review some recent biological applications of colloidal nanocrystals are

discussed, without going into biological or chemical details. First, the

properties of colloidal nanocrystals and how they can be synthesized are

described. Second, the conjugation of nanocrystals with biological molecules

is discussed. And third, three different biological applications are

introduced: (i) the arrangement of nanocrystal–oligonucleotide conjugates

using molecular scaffolds such as single-stranded DNA, (ii) the use of

nanocrystal–protein conjugates as fluorescent probes for cellular imaging,

and (iii) a motility assay based on the uptake of nanocrystals by living cells.

Laura Mazzola(2003) “Commercializing nanotechnology” Nature Biotechnology 21, 1137 -

1143 (2003). Nanotechnology has solid commercial prospects, but the process of

converting basic discoveries into marketable products will be long and hard.

Nanotechnology has been showcased and revisited a number of times over the

past decade, with each pass hinting at the promise of a revolutionary, ubiquitous

technology. The editors of Sciencemagazine fell under its spell in 2001, when

they declared nanoelectronic circuits the breakthrough of the year.

Robert Paull, Josh Wolfe, Peter Hébert & Michael Sinkula(2003) “Investing in nanotechnology”

Nature Biotechnology 21, 1144 - 1147 (2003).The current commercial path for

nanotechnology ventures mirrors the early evolution of the biotechnology

industry, allowing similar strategies toward both technology commercialization

and investment opportunities.The emergence of nanotechnology and its

commercialization has followed a similar path to the emergence of recombinant

technology and the biotechnology industry. Clear parallels can be drawn

concerning the role of the US federal government and intellectual property (IP) in

driving nanotechnology's growth.

T. Andrew Taton (2002) Dept of Chemistry, University of Minnesota, 207 Pleasant Street SE,

Minneapolis, MN 55455, USA “Nanostructures as tailored biological probes”.

A new generation of spectroscopic dyes is gradually becoming available to

biological researchers, from an unexpected source: materials chemists who study

the synthesis and properties of nano-sized inorganic objects. Research into

tailoring the optical properties, surface chemistry and biocompatibility of metallic

and semiconductor nanoparticles, exemplified in part by a recent report by

Mirkin, Schatz and coworkers, is fulfilling the promise of these nanostructures as

customizable substitutes for organic molecular probes.

George M Whitesides (2003) “The 'right' size in nanobiotechnology” Nature Biotechnology 21,

1161 - 1165 (2003) Published online: 30 September 2003. The biological and

physical sciences share a common interest in small structures (the definition of

'small' depends on the application, but can range from 1 nm to 1 mm). A vigorous
 trade across the borders of these areas of science is developing around new

materials and tools (largely from the physical sciences) and new phenomena

(largely from the biological sciences). The physical sciences offer tools for

synthesis and fabrication of devices for measuring the characteristics of cells and

sub-cellular components, and of materials useful in cell and molecular biology;

biology offers a window into the most sophisticated collection of functional

nanostructures that exists.

REVIEW ARTICLE
Q A Pankhurst, J Connolly, S K Jones and J Dobson (2001) Vol. 301 no. 5641 pp. 1882-1884

“Applications of magnetic nanoparticles in biomedicine”.The physical principles

underlying some current biomedical applications of magnetic nanoparticles are

reviewed. Starting from well-known basic concepts, and drawing on examples

from biology and biomedicine, the relevant physics of magnetic materials and

their responses to applied magnetic fields are surveyed. The way these properties

are controlled and used is illustrated with reference to (i) magnetic separation of

labelled cells and other biological entities; (ii) therapeutic drug, gene and

radionuclide delivery; (iii) radio frequency methods for the catabolism of tumours

via hyperthermia; and (iv) contrast enhancement agents for magnetic resonance

imaging applications.

Hao Yan1,Sung Ha Park,Gleb Finkelstein, John H. Reif and Thomas H. LaBean (2003)

“DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive

Nanowires” A DNA nanostructure consisting of four four-arm junctions oriented

with a square aspect ratio was designed and constructed. Programmable self-
 assembly of 4 × 4 tiles resulted in two distinct lattice morphologies: uniform-

width nanoribbons and two-dimensional nanogrids, which both display periodic

square cavities. Periodic protein arrays were achieved by templated self-assembly

of streptavidin onto the DNA nanogrids containing biotinylated oligonucleotides.

On the basis of a two-step metallization procedure, the 4 × 4 nanoribbons acted as

an excellent scaffold for the production of highly conductive, uniform-width,

silver nanowires.

Kinneret Keren1, Rotem S. Berman1 and Evgeny Buchstab (1998) Department of Physics,

Technion-Israel Institute of Technology, Haifa 32000, Israel. "DNA-Templated

Carbon Nanotube Field-Effect Transistor" Science 25 September 1998: Vol. 281

no. 5385 pp. 2013-2016 DOI: 10.1126/science.281.5385.2013. The combination

of their electronic properties and dimensions makes carbon nanotubes ideal

building blocks for molecular electronics. However, the advancement of carbon

nanotube–based electronics requires assembly strategies that allow their precise

localization and interconnection. Using a scheme based on recognition between

molecular building blocks, we report the realization of a self-assembled carbon

nanotube field-effect transistor operating at room temperature. A DNA scaffold

molecule provides the address for precise localization of a semiconducting single-

wall carbon nanotube as well as the template for the extended metallic wires

contacting it.
Marcel Bruchez Jr., Mario Moronne, Peter Gin, Shimon Weiss and A. Paul Alivisatos(1998)

Department of Chemistry, University of California, Berkeley, CA 94720,

"Semiconductor Nanocrystals as Fluorescent Biological Labels" Science 25

September 1998: Vol. 285 no. 5387 pp. 2028-2030 Semiconductor nanocrystals

were prepared for use as fluorescent probes in biological staining and diagnostics.

Compared with conventional fluorophores, the nanocrystals have a narrow,

tunable, symmetric emission spectrum and are photochemically stable. The

advantages of the broad, continuous excitation spectrum were demonstrated in a

dual-emission, single-excitation labeling experiment on mouse fibroblasts. These

nanocrystal probes are thus complementary and in some cases may be superior to

existing fluorophores.

Shaopeng Wang, Natalia Mamedova, Nicholas A. Kotov, Wei Chen, and Joe Studer (2002)
Nomadics Inc., 1024 S Innovation Way, Stillwater, Oklahoma 74074, Nano Letters, 2002, 2 (8),
pp 817–822 DOI: 10.1021/nl0255193 Publication Date (Web): July 19, 2002.Complementary
bioconjugates based on antibody−antigen interactions were synthesized from luminescent CdTe
nanoparticles (NPs). Antigen (bovine serum albumin) was conjugated to red-emitting CdTe NPs,
while green-emitting NPs were attached to the corresponding anti-BSA antibody (IgG). The NP
bioconjugates were characterized by native and SDS−PAGE electrophoresis, gel-permeation
HPLC, and circular dichroism. Antigen−antibody binding affinity was evaluated by enzyme-
linked immunosorbent assay (ELISA). The formation of BSA−IgG immunocomplex resulted in
the Förster resonance energy transfer (FRET) between the two different NPs: the luminescence
of green-emitting NPs was quenched whereas the emission of the red-emitting NPs was
enhanced. The luminescence recovered when the immunocomplex was exposed to an unlabeled
antigen. The immunocomplexes can be considered as a prototype of NP superstructures based on
biospecific ligands, while the competitive FRET inhibition can be used in an immunoassay
protocol.

Julia V Georgieva, Dharamdajal Kalicharan, Pierre-Olivier Couraud, Ignacio A Romero,

Babette Weksler, Dick Hoekstra and Inge S Zuhorn (2001) “Surface Characteristics of
Nanoparticles Determine Their Intracellular Fate in and Processing by Human Blood–Brain
Barrier Endothelial Cells In Vitro”.A polarized layer of endothelial cells that comprises the
blood–brain barrier (BBB) precludes access of systemically administered medicines to brain
tissue. Consequently, there is a need for drug delivery vehicles that mediate transendothelial
transport of such medicines. Endothelial cells use a variety of endocytotic pathways for the
internalization of exogenous materials, including clathrin-mediated endocytosis, caveolar
endocytosis, and macropinocytosis. The different modes of endocytosis result in the delivery of
endocytosed material to distinctive intracellular compartments and therewith correlated
differential processing. To obtain insight into the properties of drug delivery vehicles that direct
their intracellular processing in brain endothelial cells, we investigated the intracellular
processing of fixed-size nanoparticles in an in vitro BBB model as a function of distinct
nanoparticle surface modifications. Caveolar endocytosis, adsorptive-mediated endocytosis, and
receptor-mediated endocytosis were promoted by the use of uncoated 500-nm particles,
attachment of the cationic polymer polyethyleneimine (PEI), and attachment of prion proteins,
respectively. We demonstrate that surface modifications of nanoparticles, including charge and
protein ligands, affect their mode of internalization by brain endothelial cells and thereby their
subcellular fate and transcytotic potential.

Davide Pantarotto, Charalambos D. Partidos, Johan Hoebeke, Fred Brown, Ed

Kramer3, Jean-Paul Briand1, Sylviane Muller1, Maurizio Prato2 and Alberto Bianco
1
Institut de Biologie Moléculaire et Cellulaire, UPR 9021 CNRS, Immunologie et Chimie
Thérapeutiques, 15 Rue René Descartes, 67084 Strasbourg, France
2
Dipartimento di Scienze Farmaceutiche, Università di Trieste, Piazzale Europa 1, 34127
Trieste, Italy
3
United States Department of Agriculture, Plum Island Animal Disease Center, Agricultural
Research Service, Greenport, NY 11944 USA

Abstract
• Functionalized carbon nanotubes (CNTs) hold a lot of promise for application in
medicinal chemistry. Based on a method for preparation of water-soluble CNTs, we
covalently linked a neutralizing B cell epitope from the foot-and-mouth disease virus
(FMDV) to mono- and bis-derivatized CNTs. Immunological characterization of these
conjugates revealed that the epitope was appropriately presented after conjugation to
CNTs for recognition by antibodies as measured by BIAcore technology. Moreover,
peptide-carbon nanotubes elicited strong anti-peptide antibody responses in mice with no
detectable cross-reactivity to the carbon nanotubes. However, only the mono-derivitized
CNT conjugate induced high levels of virus-neutralizing antibodies. These findings
highlight for the first time the potential of CNTs to present biologically important
epitopes in an appropriate conformation both in vitro and in vivo and open up the
possibility for their use in vaccine delivery.
 The BARC biosensor applied to the detection of biological warfare agents

R. L. Edelstein , a, C. R. Tamanahab, P. E. Sheehanb, M. M. Millerb, D. R. Baselt1, , b, L. J.

Whitmanb and R. J. Coltonb
a
Geo-Centers, Inc., PO Box 441340, Fort Washington, MD 20749-1340, USA
b
Naval Research Laboratory, 4555 Overlook Ave., SW, Washington, DC 20375, USA
Received 1 July 1999;
revised 12 September 1999;
accepted 17 September 1999.
Available online 24 January 2000.

Abstract
The Bead ARray Counter (BARC) is a multi-analyte biosensor that uses DNA hybridization,
magnetic microbeads, and giant magnetoresistive (GMR) sensors to detect and identify
biological warfare agents. The current prototype is a table-top instrument consisting of a
microfabricated chip (solid substrate) with an array of GMR sensors, a chip carrier board with
electronics for lock-in detection, a fluidics cell and cartridge, and an electromagnet. DNA probes
are patterned onto the solid substrate chip directly above the GMR sensors, and sample analyte
containing complementary DNA hybridizes with the probes on the surface. Labeled, micron-
sized magnetic beads are then injected that specifically bind to the sample DNA. A magnetic
field is applied, removing any beads that are not specifically bound to the surface. The beads
remaining on the surface are detected by the GMR sensors, and the intensity and location of the
signal indicate the concentration and identity of pathogens present in the sample. The current
BARC chip contains a 64-element sensor array, however, with recent advances in
magnetoresistive technology, chips with millions of these GMR sensors will soon be
commercially available, allowing simultaneous detection of thousands of analytes. Because each
GMR sensor is capable of detecting a single magnetic bead, in theory, the BARC biosensor
should be able to detect the presence of a single analyte molecule.

Author Keywords: Biosensor; Magnetoresistive technology; DNA patterning; DNA

hybridization; Magnetic beads; Fluidics

Science 26 September 2003:

Vol. 301 no. 5641 pp. 1884-1886
DOI: 10.1126/science.1088755

• REPORT

Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins

1. Jwa-Min Nam*,
2. C. Shad Thaxton* and
 3. Chad A. Mirkin†
+Author Affiliations
1. Department of Chemistry and Institute for Nanotechnology, Northwestern University,
2145 Sheridan Road, Evanston, IL 60201, USA
1. † To whom correspondence should be addressed. E-
mail: camirkin@chem.northwestern.edu
• ↵* These authors contributed equally to the work.
ABSTRACT

An ultrasensitive method for detecting protein analytes has been developed. The system
relies on magnetic microparticle probes with antibodies that specifically bind a target of
interest [prostate-specific antigen (PSA) in this case] and nanoparticle probes that are
encoded with DNA that is unique to the protein target of interest and antibodies that can
sandwich the target captured by the microparticle probes. Magnetic separation of the
complexed probes and target followed by dehybridization of the oligonucleotides on the
nanoparticle probe surface allows the determination of the presence of the target protein
by identifying the oligonucleotide sequence released from the nanoparticle probe. Because
the nanoparticle probe carries with it a large number of oligonucleotides per protein
binding event, there is substantial amplification and PSA can be detected at 30 attomolar
concentration. Alternatively, a polymerase chain reaction on the oligonucleotide bar codes
can boost the sensitivity to 3 attomolar. Comparable clinically accepted conventional assays
for detecting the same target have sensitivity limits of ∼3 picomdar, six orders of
magnitude less sensitive than what is observed with this method.

Biomimetic processing of nanocrystallite bioactive apatite coating on titanium

Author
J Ma1,3, Huifen Wong1, L B Kong1,4 and K W Peng2
Affiliations
1
School of Materials Engineering, Nanyang Technological University, Singapore
2
Molecular Medicine Program, Mayo Foundation, Rochester, MN 55905, USA
3
Author to whom any correspondence should be addressed.
4
Present address: Temasek Laboratory, National University of Singapore, 10 Kent Ridge
Cresent, 119260 Singapore.
E-mail
asjma@ntu.edu.sg
Journal
Nanotechnology Create an alert RSS this journal
Issue
Volume 14, Number 6
Citation
J Ma et al 2003 Nanotechnology 14 619
doi: 10.1088/0957-4484/14/6/310

ArticleReferencesCited By

Tag this article Full text PDF (438 KB)

Abstract
Biomimetic processes have attracted huge attention in recent years due to their
significant applications in biomedical areas such as bone tissue engineering. In the
present study, a biomimetic process was employed to form a nanocrystallite apatite
coating on metal. A thin bone-like apatite layer was coated onto titanium (Ti) metals
via an alkali pre-treatment. This was followed by immersion in a simulated body fluid.
Analysis of the coating by thin film x-ray diffraction and scanning electron
microscope has shown that the apatite layer grown in this way exhibits nanostructure
and has similar stoichiometry to that of natural bone. It is observed that the thickness
of the apatite layer increases as the immersion period increases. The growth kinetics
and mechanism are also discussed. A cross-sectional study has also shown that a
uniform coating of carbonate-containing apatite (hydroxyapatite) is firmly adhered on
the Ti metal. The adhesion of the apatite layer on the Ti substrate was further
confirmed by a shear test, which has shown an average value of 9.5 MPa. The
bioactivity of the coating was finally examined by cell culturing experiments. The
results have shown that the nanocomposite prepared using the present method
possesses good mechanical properties and bioactivity.
Immunospecific ferromagnetic iron-dextran reagents for the labeling and magnetic
separation of cells

Robert S. Moldaya and Donald Mackenziea

a
Department of Biochemistry, University of British Columbia, Vancouver, B.C. V6T 1W5,
Canada
Received 28 September 1981;
accepted 25 January 1982.
Available online 12 November 2002.
Abstract
Ferromagnetic iron dextran particles were prepared by reacting a mixture of ferrous chloride and
ferric chloride with dextran polymers under alkaline conditions. Particles purified by gel
filtration chromatography were in the size range of 30–40 nm, had an electron dense core of
about 15 nm, were stable against aggregation in physiological buffer, showed little non-specific
binding to cells and had a magnetic moment. Protein A from Staphylococcus aureus was
covalently coupled to periodate-oxidized ferromagnetic iron-dextran particles. These conjugates
were used to indirectly label antigen sites on human red blood cells and thymocytes for
visualization by scanning and transmission electron microscopy. Cells labeled with these
immunospecific ferromagnetic particles were quantitatively retained by a simple permanent
magnet and could be separated from unlabeled cells. Applications of these novel reagents in the
separation of cells, cell membranes and receptors and in drug targeting studies are discussed.

Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast

agents for MR imaging.
Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, Josephson L.
Department of Radiology, Massachusetts General Hospital, Boston.
Abstract
An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small
enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate
pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm.
The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger
superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy
demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular
transport and through interendothelial junctions. Twenty-four hours after intravenous
administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per
gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential
applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a
bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the
magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance
imaging.

Cell Motility and Metastatic Potential Studies Based on Quantum Dot Imaging of
Phagokinetic Tracks
1. W.J. Parak1,
2. R. Boudreau3,
 3. M. Le Gros4,
4. D. Gerion1,
5. D. Zanchet2,
6. C.M. Micheel2,
7. S.C. Williams2,
8. A.P. Alivisatos1,
9. C. Larabell3
Article first published online: 17 JUN 2002

The uptake of colloidal semiconductor nanocrystals by a large range of eukaryotes (see

Figure) is directly correlated with the cell motility, as has been shown by comparing the motions
of cancerous and healthy human breast cells. The nanocrystals are more photochemically robust
than organic dyes and provide a powerful tool for studying the processes of cell motility and
migration—behaviors that are responsible for metastases of primary cancers.

Collagen Coating Promotes Biocompatibility of Semiconductor Nanoparticles in Stratified

LBL Films
• Abstract
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• Citing Articles
Vladimir A. Sinani,† Dmitry S. Koktysh,† Bo-Geon Yun,‡ Robert L. Matts,‡ Todd C.
Pappas,§ Massoud Motamedi,§ Stephanie N. Thomas,† and Nicholas A. Kotov*†
Department of Chemistry and Department of Biochemistry and Molecular Biology, Oklahoma
State University, Stillwater, Oklahoma 74078, and Center for Biomedical Engineering,
University of Texas Medical Branch, Galveston, Texas 77550
Nano Letters, 2003, 3 (9), pp 1177–1182
DOI: 10.1021/nl0255045
Publication Date (Web): August 6, 2003
Copyright © 2003 American Chemical Society
Nanostructured thin films fabricated from semiconductor nanoparticles (NPs) are of great
interest for biomedical applications, but NP materials based on heavy metals can be cytotoxic. In
this work, the preparation of semiconductor NPs followed the protocol of layer-by-layer (LBL)
assembly, which alleviates this problem. Collagen/poly(acrylic acid) bilayers were added to
CdTe/polycation LBL films to produce porous collagen bilayers. Such stratified multilayer
systems showed successful cell attachment and survival while native NP films were strongly
cytotoxic.