Quantum dots incorporated magnetic nanoparticles for imaging colon carcinoma cells


201306047919620Engineered multifunctional nanoparticles (NPs) have made a tremendous impact on the biomedical sciences, with advances in imaging, sensing and bioseparation. In particular, the combination of optical and magnetic responses through a single particle system allows us to serve as novel multimodal molecular imaging contrast agents in clinical settings.

Despite of essential medical imaging modalities and of significant clinical application, only few nanocomposites have been developed with dual imaging contrast. A new method for preparing quantum dots (QDs) incorporated magnetic nanoparticles (MNPs) based on layer-by-layer (LbL) self-assembly techniques have developed and used for cancer cells imaging.

Methods:  Here, citrate – capped negatively charged Fe3O4 NPs were prepared and coated with positively – charged hexadecyltrimethyl ammonium bromide (CTAB).

Then, thiol – capped negatively charged CdTe QDs were electrostatically bound with CTAB. Morphological, optical and magnetic properties of the fluorescent magnetic nanoparticles (FMNPs) were characterized.

Prepared FMNPs were additionally conjugated with hCC49 antibodies fragment antigen binding (Fab) having binding affinity to sialylated sugar chain of TAG-72 region of LS174T cancer cells, which was prepared silkworm expression system, and then were used for imaging colon carcinoma cells.

Results:  The prepared nanocomposites were magnetically responsive and fluorescent, simultaneously that are useful for efficient cellular imaging, optical sensing and magnetic separation. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the particle size is around 50 nm in diameter with inner magnetic core and outer CdTe QDs core-shell structure.

Cytotoxicity test of prepared FMNPs indicates high viability in Vero cells. NPs conjugated with anti cancer antibodies were successfully labeled on colon carcinoma cells (LS174) in vitro and showed significant specificity to target cells.

Conclusion:  The present report demonstrates a simple synthesis of CdTe QDs-Fe3O4 NPs.

The surface of the prepared FMNPs was enabled simple conjugation to monoclonal antibodies by electrostatic interaction. This property further extended their in vitro applications as cellular imaging contrast agents.

Such labeling of cells with new fluorescent-magneto nanoprobes for living detection is of interest to various biomedical applications and has demonstrated the potential for future medical use.

Author: Syed Rahin AhmedJinhua DongMegumi YuiTatsuya KatoJaebeom LeeEnoch Y Park
Credits/Source: Journal of Nanobiotechnology 2013, 11:28

New Report on Graphene goes “Beyond the Hype


201306047919620A new report due to be published this month by Cientifica gets beneath the layers of hype that posit graphene at the top of a pile of wonder materials, promising interesting reading for anyone wanting a real-world evaluation of graphene and its chances of success.

Graphene is touted as teh next wonder material, but can it live up to the hype?

Three years after announcing a substantial capacity increase to its multi-walled carbon nanotube (MWNT) production, Germany‘s Bayer Material Science recently announced that it was completely shutting down its MWNT production. The arms race into nanomaterials capacity-building that began almost a decade ago has, today, amounted to a stockpile of excess product. Nanomaterials, like fullerenes and nanotubes, are now much cheaper due to oversupply, but this matters little because there are no applications to create demand, and the ones that do exist require very small quantities compared with current capacity.

Cientifica’s upcoming Graphene Opportunity Report, takes a similar stance to the UK company’s first edition Nanotechnology Opportunity Report published a decade ago. The report countered the predictions at the time of a trillion-dollar market and a revolution across manufacturing industries, which have largely failed to materialize. Like the Nanotechnology Opportunity Report, the Graphene Opportunity Report purports the real value to be in applications, which means for companies setting themselves up as materials suppliers, most will need to ascend the value chain, developing applications that can exploit their materials and resulting products be it powders, dispersions and even inks.

Hype pitfalls

‘There are something like a hundred graphene companies, or more, worldwide. For materials suppliers that are aiming to make graphene by the multi-tonne quantity, where there are as yet no applications developed, this industry risks going through a similar hype bubble that nanotubes and other nanomaterials sectors have been through,’ says Tim Harper, founder of Cientifica.

A strong point for graphene lies in its ability to be processed as an ink, making it potentially compatible with plastic, or organic, electronics: a group of nanomaterials that can be used to fabricate devices by solution-processable techniques. The plastic electronics industry has gone through its own cycle of hype but is making steady headway so there might be opportunities for graphene to leverage progress made so far and benefit plastic electronics in return. But, as Harper warns, new materials are only taken up into production if they offer a cheaper process to the incumbent one they aim to replace, or they offer far superior performance.

New process to make nanospheres could enable advances across multiple industries


QDOTS imagesCAKXSY1K 8(Nanowerk News) A patent-pending technology to produce  nanospheres developed by a research team at North Dakota State University,  Fargo, could enable advances across multiple industries, including electronics,  manufacturing, and biomedical sectors.

 

The environmentally-friendly process produces polymer-based  nanospheres (tiny microscopic particles) that are uniform in size and shape,  while being low-cost and easily reproducible. The process developed at NDSU  allows scale-up of operation to high production levels, without requiring  specialized manufacturing equipment.

NANOSPHERES
The environmentally-friendly process oxidizes ozone in water to produce  polymer-based nanospheres, ranging from 70 to 400 nanometers in diameter, that  are uniform in size and shape, stay suspended in solution, and are easily  removed using a centrifuge. The scanning electron microscopy image depicts the  uniform spherical morphology of these nanospheres.

A 3 a.m. Eureka! moment

Dr. Victoria Gelling, associate professor in the Department of  Coatings and Polymeric Materials at NDSU, had a “Eureka!” moment when she woke  early one morning – 3 a.m., to be precise, an hour when most of us are still  sleeping. Dr. Gelling used early morning creativity to imagine a new way to  oxidize monomers, which are relatively small and simple molecules, into  polymers, which are larger, more complex molecules that can be used to create  synthetic materials. Dr. Gelling hypothesized that oxidizing ozone in water  might accomplish this task.

Later that day in the lab, Dr. Gelling and her team tested the  hypothesis. On the first try, they created a suspension of nearly perfectly  rounded, uniformly-sized nanospheres, ranging from 70 to 400 nanometers in  diameter. In addition to their uniform size, the nanospheres stay suspended in  the solution, and are easily removed using a centrifuge.

“The synthesis of the nanospheres is rather simple, with no  other chemicals required other than water, ozone, and the small molecules which  will become the polymers,” said Dr. Gelling. “We also have tight control of the  size, as they are beautiful, perfect marbles.”

Given their uniform size and shape, the nanospheres could have  uses across multiple industries. According to Dr. Gelling, such nanospheres  could be used to:

  • Produce  high-performance electronic devices and energy-efficient digital displays
  • Create  materials with high conductivity and smaller parts for consumer electronics
  • Deliver  medicine directly to diseased cells in the body
  • Provide  antibacterial coating on dressing for wounds
  • Develop  nanosensors to aid in early disease detection
  • Create  coatings that provide increased protection against corrosion and  abrasion

Watch the Video Here: http://youtu.be/ndK-NzULfAk

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Nanotechnology applications and nanomaterials are being applied across a raft of industries


QDOTS imagesCAKXSY1K 8DUBLIN–(BUSINESS WIRE)–

Research and Markets (http://www.researchandmarkets.com/research/9g39vg/the_global)       has announced the addition of the “The       Global Nanotechnology and Nanomaterials Industry: Stage of Development,       Global Activity and Market Opportunities” report to their       offering.

Nanotechnology applications and nanomaterials are being applied across a raft of industries due to their outstanding magnetic, optical, catalytic and electronic properties. There are already established market for nanomaterials including titanium dioxide, zinc oxide, silicon oxide nanopowders and carbon nanotubes, nanofibers, nanosilver, nanoclays, quantum dots and nanoporous materials driven by demand from applications in filtration, electronics, cosmetics, energy, medicine, chemicals, coatings and catalysts. Recent breakthroughs have heralded new market opportunities in graphene and nanocellulose. This new 696-page report from Future Market, Inc., the world’s leading provider of nanotechnology and nanomaterials information and publisher of Nanotech Magazine,  provides a comprehensive insight into all aspects of the market for these materials.

WHAT DOES THE REPORT INCLUDE?

– Comprehensive data and forecasts for the global nanotechnology and nanomaterials market to 2019. Nanomaterials covered include aluminium  oxide nanopowders, antimony tin, bismuth oxide, carbon nanotubes, cerium oxide, cobalt oxide, fullerenes and POSS, graphene, graphyne, graphdiyne, graphane, indium, iron oxide, magnesium oxide, manganese oxide, molybdenum disulphide, nanocellulose, nanoclays, nanofibers, nanosilver, nickel oxide, nano-precipitated calcium carbonate, nanoporous materials, quantum dots, silicone, silicon oxide, titanium dioxide, yttrium oxide, zinc oxide and zirconium oxide

– Technology roadmaps/commercialization timelines to 2019, by       nanomaterials and by market

– Financial estimates for the markets nanotechnology and nanomaterials will impact including aerospace and aviation, automotive, civil engineering and construction, exterior protection, communications, hygiene, cleaning and sanitary, electronics and semiconductors, energy, environment, food, agricultural, beverage, marine, medical and life sciences, military and defence, packaging, paper, personal care, plastics and rubber, printing, product security and anti-counterfeiting, sensors, sporting and consumer goods, textiles, tools and metals

– Latest global regulations for nanomaterials

– Patent analysis

– Global government funding and programmes

– Nanomaterials market size by tons and by end user demand

– Over 500 tables and figures

– Over 1000 company and research centre profiles.

Key Topics Covered:

1 EXECUTIVE SUMMARY

2 METHODOLOGY

3 NANOMATERIALS PRODUCTION: CURRENT AND PROJECTED

  •         3.1 Applications of nanomaterials
  •         3.2 Production estimates 2012
  •         3.3 Demand by material type and market
  •         3.4 ALUMINIUM OXIDE
  •         3.5 ANTIMONY TIN OXIDE
  •         3.6 BISMUTH OXIDE
  •         3.7 CARBON NANOTUBES
  •         3.8 CERIUM OXIDE
  •         3.9 COBALT OXIDE
  •         3.10 COPPER OXIDE
  •         3.11 FULLERENES AND POSS
  •         3.12 GRAPHENE
  •         3.13 GRAPHYNE
  •         3.14 GRAPHDIYNE
  •         3.15 GRAPHANE
  •         3.16 INDIUM
  •         3.17 IRON OXIDE
  •         3.18 MAGNESIUM OXIDE
  •         3.19 MANGANESE OXIDE
  •         3.20 MOLYBDENUM DISULFIDE
  •         3.21 NANOCELLULOSE
  •         3.22 NANOCLAYS
  •         3.23 NANOFIBERS
  •         3.24 NANO-PRECIPITATED CALCIUM CARBONATE
  •         3.25 NANOSILVER
  •         3.26 NICKEL OXIDE
  •         3.27 NANOPOROUS MATERIALS
  •         3.28 QUANTUM DOTS
  •         3.29 SILICENE
  •         3.30 SILICON OXIDE

4 LICENSING AGREEMENTS/PARTNERSHIPS

  •         4.1 Aerospace and aviation
  •         4.2 Automotive
  •         4.3 Civil engineering, construction and exterior protectioon
  •         4.4 Communications
  •         4.5 Hygiene, cleaning and sanitary
  •         4.6 Electronics
  •         4.7 Energy
  •         4.8 Environment
  •         4.9 Food, agriculture and beverage
  •         4.10 Marine
  •         4.11 Medical and life sciences
  •         4.12 Military and defence
  •         4.13 Packaging
  •         4.14 Paper
  •         4.15 Personal care
  •         4.16 Plastics and rubber
  •         4.17 Printing
  •         4.18 Product security and anti-counterfeiting
  •         4.19 Sensors
  •         4.20 Sporting and consumer goods
  •         4.21 Textiles
  •         4.22 Tools and metals

5 REGULATIONS

6 PATENT ACTIVITY

7 GLOBAL FUNDING AND GOVERNMENT INITIATIVES

8 MARKETS FOR NANOTECHNOLOGY AND NANOMATERIALS

  •         8.1 ADHESIVES AND SEALANTS
  •         8.2 AEROSPACE AND AVIATION
  •         8.3 AUTOMOTIVE
  •         8.4 COMMUNICATIONS
  •         8.5 CIVIL ENGINEERING, CONSTRUCTION AND EXTERIOR PROTECTION
  •         8.6 HYGIENE, CLEANING AND SANITARY INCLUDING HOMEWARE
  •         8.7 ELECTRONICS AND PHOTONICS
  •         8.8 ENERGY
  •         8.9 ENVIRONMENT
  •         8.10 FOOD, AGRICULTURE AND BEVERAGE
  •         8.11 MARINE
  •         8.12 MEDICAL AND LIFE SCIENCES
  •         8.13 MILITARY AND DEFENCE
  •         8.14 PACKAGING
  •         8.15 PAPER
  •         8.16 PERSONAL CARE
  •         8.17 PLASTICS AND RUBBER
  •         8.18 PRINTING
  •         8.19 PRODUCT SECURITY AND ANTI-COUNTERFEITING
  •         8.20 SENSORS
  •         8.21 SPORTING AND CONSUMER GOODS
  •         8.22 TEXTILES
  •         8.23 TOOLS AND METALS

9 REFERENCES

For more information visit http://www.researchandmarkets.com/research/9g39vg/the_global

 

Contact:
Research and Markets Laura Wood, Senior Manager.

Nanoparticles for Molecular Imaging


by Professor Andrew Tsourkas

Professor Andrew Tsourkas, Cellular and Molecular Imaging LabDepartment of BioengineeringUniversity of Pennsylvania
Corresponding author: atsourk@seas.upenn.edu

Over the past decade there has been an explosion in the number of nanotechnology-based agents that have been applied to biological and medical applications. It is generally believed that these agents will revolutionize how medicine is practiced. One particularly promising direction that has garnered a great deal of interest is molecular imaging.

The development of nanotechnology-based imaging probes offers to substantially improve the specificity and sensitivity of diagnostic imaging by allowing for the non-invasive and quantitative detection of specific biomolecules in living subjects.

In general, molecular imaging probes consist of a nanoparticle that has been functionalized with a targeting agent. The targeting agent is typically selected to recognize a disease biomarker located on the cell surface;1-4 however, probes have also been developed that strictly bind healthy tissue, thus leaving malignancies within target tissues unlabeled.5-7 In either case, the nanoparticles serve to enhance the contrast between malignant and benign tissue.

Interest in the use of nanoparticles stems from their ability to provide improved contrast compared with more traditional contrast agents and the ability to control their pharmacokinetics through variations of their size, surface properties, and shape.8 The strong contrast enhancing capabilities of nanoparticles can typically be attributed to atomic constraints that occur at the nanometer size-scale and/or the cumulative effect that results from packing many contrast agents into nanometer-sized particles.

For example, when iron oxide particles are synthesized at the nanometer-size scale they exhibit “superparamagnetic” properties because they can exist as single-domain crystals. In contrast, larger iron oxide particles generally consist of multiple magnetic domains that are aligned in the short range, but at longer distances the domains are anti-aligned and thus exhibit a reduced net magnetic effect per iron ion.

As a result, on a per iron ion basis, nano-sized iron oxide particles are generally able to generate more contrast on magnetic resonance images than larger micron-sized nanoparticles. Of course, the total iron content cannot be ignored. Since, micron-sized iron oxide particles are composed of significantly more iron ions than nanoparticles, they exhibit much stronger MR contrast on a per particle basis. This has allowed single micron-sized particles to be imaged via MR.9

To date, most nanoparticles that have been developed for magnetic resonance imaging applications have been characterized in terms of their relaxivity per ion (e.g. Fe, Gd, etc). Although this is certainly of great value, it can be argued that for molecular imaging applications it is even more important to calculate relaxivity on a per particle basis. For example, if a tumor cell has ten receptors on its surface, the binding of ten micron-sized particles of iron oxide would certainly provide more contrast than ten nanoparticles, even though the smaller nanoparticles would likely have a higher relaxivity per iron ion than the micron-sized particle.

This argument is, of course, not limited to iron oxide particles. A recent comparison that we made between Gd-labeled dendrimers and Gd-labeled dendrimer nanoclusters (DNCs) also highlights the importance of calculating the relaxivity per nanoparticle.1 In this study, Gd-labeled DNCs were formed by simply cross-linking Gd-labeled dendrimers into a higher-order structure, with a mean hydrodynamic diameter of ~150nm. While both the dendrimers and DNCs exhibited a similar relaxivity per Gd ion, the DNCs possessed >1,000-times more Gd per particle. As a result of this higher payload, the tumor-targeted Gd-labeled DNCs provided a dramatic improvement in contrast compared with Gd-labeled dendrimers, in tumor-bearing mice.

Aside from the contrast-enhancing capabilities of molecular imaging agents, it is also of critical importance to characterize the pharmacokinetics of new nanoparticle formulations. Particle size, shape, and charge are all known to be major driving forces responsible for dictating the blood half-life and biodistribution.

In general, nanoparticles at the length scale of ~10-100nm have generally exhibited longer circulations times and improved tissue penetration than micron-sized particles. These pharmacokinetic properties can lead to improved targeting and in many cases can be used to overcome the lower contrast-enhancing capabilities of smaller particles – hence the growing interest in using nanoparticles as opposed to micron-sized particle for molecular imaging applications.

In applications where long circulation times and additional contrast is not necessary, there has even been a movement to make molecular imaging probes that are <5.5nm in diameter to encourage renal filtration.10 This would allow for more rapid imaging, since unbound nanoparticles would be cleared much faster, and reduced toxicity for the same reasons.

In addition to the physical-chemical properties of the nanoparticle itself, the targeting agent also plays an instrumental role in the utility of nanoparticle-based contrast agents. For the most part, targeting agents that have been evaluated for molecular imaging applications have mirrored those used for targeted therapeutics (e.g. folic acid, transferrin, anti-HER2/neu antibodies, etc.).

For cancer imaging, these agents have shown a great deal of promise when used to assess the availability of therapeutic targets and monitor the efficacy of treatment; however, tumor cell receptors are unlikely to be adopted for diagnostic imaging due to the lack of any single receptor that is highly up-regulated across most tumors.

For diagnostic imaging, a biomarker that is universally present would have to be identified for clinical utility. Borrowing from FDG-PET imaging, one option that is being explored involves taking advantage of the increased metabolic rate of cancer cells and the resultant acidic microenvironment. Accordingly, various agents are being developed that specifically bind to cells that exist in subphysiologic pH.11 Since, an acidic microenvironment is common to most tumors, it is expected that tumor pH could serve as a more universal target. Ligands that target angiogeneisis or hypoxia could also potentially be utilized to expand the versatility of targeted molecular imaging probes. Of course, when biomarkers with increased universality are selected, it often comes at the cost of reduced specificity – a criticism that has often plagued FDG-PET.

In conclusion, nanoparticles have shown great promise as molecular imaging probes. However, as the number of nanoparticle formulations continues to expand it will be increasingly important to establish proper indices by which they can be compared. It will also be important to develop creative targeting strategies that can be used to identify disease with high sensitivity and high predictive value.


References

1. Cheng Z, Thorek DL, Tsourkas A. Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent. Angew Chem Int Ed Engl. 2010;49(2):346-50.
2. Thorek DL, Chen AK, Czupryna J, Tsourkas A. Superparamagnetic iron oxide nanoparticle probes for molecular imaging. Ann Biomed Eng. 2006 Jan;34(1):23-38.
3. Tsourkas A, Shinde-Patil VR, Kelly KA, Patel P, Wolley A, Allport JR, Weissleder R. In vivo imaging of activated endothelium using an anti-VCAM-1 magnetooptical probe. Bioconjug Chem. 2005 May-Jun;16(3):576-81.
4. Zhang CY, Lu J, Tsourkas A. Iron chelator-based amplification strategy for improved targeting of transferrin receptor with SPIO. Cancer Biol Ther. 2008 Jun;7(6):889-95.
5. Montet X, Weissleder R, Josephson L. Imaging pancreatic cancer with a peptide-nanoparticle conjugate targeted to normal pancreas. Bioconjug Chem. 2006 Jul-Aug;17(4):905-11.
6. Reimer P, Weissleder R, Shen T, Knoefel WT, Brady TJ. Pancreatic receptors: initial feasibility studies with a targeted contrast agent for MR imaging. Radiology. 1994 Nov;193(2):527-31.
7. Tanimoto A, Kuribayashi S. Hepatocyte-targeted MR contrast agents: contrast enhanced detection of liver cancer in diffusely damaged liver. Magn Reson Med Sci. 2005;4(2):53-60.
8. Moghimi SM, Hamad I. Factors Controlling Pharmacokinetics of Intravenously Injected Nanoparticulate Systems. In: de Villiers MM, Aramwit P, Kwon GS, editors. Nanotechnology in Drug Delivery. New York: Springer; 2009. p. 267-82.
9. Shapiro EM, Skrtic S, Sharer K, Hill JM, Dunbar CE, Koretsky AP. MRI detection of single particles for cellular imaging. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10901-6.
10. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV. Renal clearance of quantum dots. Nat Biotechnol. 2007 Oct;25(10):1165-70.
11. Reshetnyak YK, Andreev OA, Lehnert U, Engelman DM. Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6460-5.

Copyright AZoNano.com, Professor Andrew Tsourkas (University of Pennsylvania)