New theranostic nanoparticle delivers, tracks cancer drugs

201306047919620(Nanowerk News) University of New South Wales (UNSW)  chemical engineers have synthesised a new iron oxide nanoparticle that delivers  cancer drugs to cells while simultaneously monitoring the drug release in real  time.
The result, published online in the journal ACS Nano (“Using Fluorescence Lifetime Imaging Microscopy to  Monitor Theranostic Nanoparticle Uptake and Intracellular Doxorubicin  Release”), represents an important development for the emerging field of  theranostics – a term that refers to nanoparticles that can treat and diagnose  disease.
Iron oxide nanoparticles that can track drug delivery will  provide the possibility to adapt treatments for individual patients,” says  Associate Professor Cyrille Boyer from the UNSW School of Chemical Engineering.
By understanding how the cancer drug is released and its effect  on the cells and surrounding tissue, doctors can adjust doses to achieve the  best result.
Importantly, Boyer and his team demonstrated for the first time  the use of a technique called fluorescence lifetime imaging to monitor the drug  release inside a line of lung cancer cells.
“Usually, the drug release is determined using model experiments  on the lab bench, but not in the cells,” says Boyer. “This is significant as it  allows us to determine the kinetic movement of drug release in a true biological  environment.”
Magnetic iron oxide nanoparticles have been studied widely  because of their applications as contrast agents in magnetic resonance imaging,  or MRI. Several recent studies have explored the possibility of equipping these  contrast agents with drugs.
However, there are limited studies describing how to load  chemotherapy drugs onto the surface of magnetic iron oxide nanoparticles, and no  studies that have effectively proven that these drugs can be delivered inside  the cell. This has only been inferred.
With this latest study, the UNSW researchers engineered a new  way of loading the drugs onto the nanoparticle’s polymer surface, and  demonstrated for the first time that the particles are delivering their drug  inside the cells.
“This is very important because it shows that bench chemistry is  working inside the cells,” says Boyer. “The next step in the research is to move  to in-vivo applications.”
Source: University of New South Wales

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Texas A&M researchers concoct nanoparticles to soak up crude oil spills

By Darren Murph posted Sep 25th, 2013 at 10:58 PM 17


Texas A&M researchers concoct nanoparticles to soak up crude oil spills


The 2010 Deepwater Horizon may be forgotten to many, but remnants of its destruction still remain in the Gulf of Mexico. Mercifully, it appears that researchers at Texas A&M University “have developed a non-toxic sequestering agentiron oxide nanoparticles coated in a polymer mesh that can hold up to 10 times their weight in crude oil.” In layman’s terms, they’ve engineered a material that can safely soak up oil.

As the story goes, the nanoparticles “consist of an iron oxide core surrounded by a shell of polymeric material,” with the goal being to soak up leftover oil that isn’t captured using conventional mechanical means. The next step? Creating an enhanced version that’s biodegradable; as it stands, the existing particles could pose a threat if not collected once they’ve accomplished their duties.



Well-defined, magnetic shell cross-linked knedel-like nanoparticles (MSCKs) with hydrodynamic diameters ca. 70 nm were constructed through the co-assembly of amphiphilic block copolymers of PAA20b-PS280 and oleic acid-stabilized magnetic iron oxide nanoparticles using tetrahydrofuran, N,N-dimethylformamide, and water, ultimately transitioning to a fully aqueous system. These hybrid nanomaterials were designed for application as sequestering agents for hydrocarbons present in crude oil, based upon their combination of amphiphilic organic domains, for aqueous solution dispersibility and capture of hydrophobic guest molecules, with inorganic core particles for magnetic responsivity.

The employment of these MSCKs in a contaminated aqueous environment resulted in the successful removal of the hydrophobic contaminants at a ratio of 10 mg of oil per 1 mg of MSCK. Once loaded, the crude oil-sorbed nanoparticles were easily isolated via the introduction of an external magnetic field. The recovery and reusability of these MSCKs were also investigated.

These results suggest that deployment of hybrid nanocomposites, such as these, could aid in environmental remediation efforts, including at oil spill sites, in particular, following the bulk recovery phase.


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


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Nanoparticles for Molecular Imaging

by Professor Andrew Tsourkas

Professor Andrew Tsourkas, Cellular and Molecular Imaging LabDepartment of BioengineeringUniversity of Pennsylvania
Corresponding author:

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.


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, Professor Andrew Tsourkas (University of Pennsylvania)