A*STAR: Detecting Breast Cancer Using Nanoscale Polymers (Contrasting Agents & Photacoustic Imaging)


Breast Cancer Polymers 051315 exposingbreaPhotoacoustic imaging is a ground-breaking technique for spotting tumors inside living cells with the help of light-absorbing compounds known as contrast agents. A*STAR researchers have now discovered a way to improve the targeting efficacy and optical activity of breast-cancer-specific contrast agents using conjugated polymer nanoparticles.

Generating photoacoustic signals requires an ultrafast laser pulse to irradiate a small area of tissue. This sets off a series of molecular vibrations that produce ultrasonic sound waves in the sample. By ‘listening’ to the pressure differences created by the acoustic waves, researchers can reconstruct and visualize the inner structures of complex objects such as the brain and cardiovascular systems.

Diagnosing cancer with requires contrast agents that deeply penetrate tissue and selectively bind to malignant cells. In addition, they need a high optical response to near-infrared laser light, a spectral region that is particularly safe to biological materials. Traditional contrast agents have been based on gold and silver nanostructures, but the complex chemical procedures needed to optically tune these nanocompounds have left researchers looking for alternatives.

Breast Cancer Polymers 051315 exposingbrea

Photoacoustic imaging of model breast cancer cells in mice reveals that a polymer-based contrast agent can illuminate tumor sites within one hour. Credit: Dove Medical Press Limited 

Malini Olivo and her colleagues from the A*STAR Singapore Bioimaging Consortium and the A*STAR Institute of Materials Research and Engineering investigated different contrast agents based on conjugated polymers. These organic macromolecules, which contain alternating double and single carbon bonds, have delocalized electrons in their frameworks that can produce useful optical properties such as photoluminescence. The researchers identified a conjugated polymer known as PFTTQ—a compound with multiple aromatic rings, alkyl chains, sulfur and nitrogen atoms—as a promising in vivo photoacoustic agent because of its biocompatible structure and light absorption that peaks in the near-infrared range.

To direct this contrast agent to cancer cells, the team synthesized ‘dot’-like nanostructures with an inner core of PFTTQ surrounded by water-soluble polyethylene glycol chains, terminated by an outer layer of folate molecules—a vitamin that specifically binds to folate receptor proteins commonly expressed by tumors. Experiments with MCF-7 model breast implanted in mice revealed the merits of this approach: in just one hour after administering the folate–conjugated polymer dots, strong photoacoustic signals emerged from the tumor positions. The folate functionality played a critical role in this bioimaging procedure, quadrupling the photoacoustic signals compared to unmodified PFTTQ dots.

“The folate–PFTTQ nanoparticles have great potential for diagnostic imaging and other biomedical applications,” says Olivo. “We are working to expand the library of biocompatible polymers to use as molecular photoacoustic .”

Explore further: Dual-action chemical agents improve a high-resolution and noninvasive way to detect cancer

More information: “Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer.” International Journal of Nanomedicine 10, 387–397 (2015). dx.doi.org/10.2147/IJN.S73558

Quantum dots deliver vitamin D to tumors for possible inflammatory breast cancer treatment


QDOTS imagesCAKXSY1K 8February 1, 2013

The shortened daylight of a Maine winter may make for long, dark nights – but it has shone a light on a novel experimental approach to fighting inflammatory breast cancer (IBC), an especially deadly form of breast cancer.

Read more at: http://phys.org/news/2013-02-quantum-dots-vitamin-d-tumors.html#jCp

Breast Cancer Treatments  – Chat w/Our Oncology Info Experts And Learn Your Treatment Options. – cancercenter.com The new approach enlists the active form of Vitamin D3, called calcitriol, which is delivered therapeutically by quantum dots. Quantum dots are an engineered light-emitting nanoscale delivery vehicle. This new preliminary work shows the dots can be used to rapidly move high concentrations of calcitriol to targeted tumor sites where cancer cells accumulate, and also through the lymph system where the cancer spreads.

With this approach, the calcitriol can fight on multiple fronts and the targeted location can be visualized with an imaging system tracking the quantum dots. The research will be presented at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa. University of Delaware cancer researcher Anja Nohe was living in Maine when she first received funding from the Maine Cancer Foundation to determine the effect of calcitriol on breast cancer cells. Reading cancer literature helped her make connections between cancer, vitamin D, and the daylight regime of higher latitudes. “By talking with talented colleagues about these ideas, the foundation was set for the current project,” she says. After moving to the University of Delaware, she began working with Kenneth Van Golen, “an expert in the biology of IBC,” to evaluate calcitriol. Compared to other forms of breast cancer, IBC is especially difficult to treat. It has a five-year survival rate of 40% versus 87% for all other breast cancers.

A big part of what makes IBC treatment difficult is its multi-site growth pattern. Current aggressive treatments such as combinations of chemotherapy, surgery and radiation, have failed to significantly improve IBC survival rates. This early experimental work on mice is encouraging because data show calcitriol can inhibit invasion and migration of SUM149 cells, an IBC cell line. “New IBC therapies are urgently needed, which is why the goal of my work is to find a successful treatment for inflammatory breast cancer, especially one with fewer side effects,” Nohe says.

More information: Presentation #2953-Pos, “Using calcitriol conjugated quantum dots to target inflammatory breast cancer tumors and metastasis in vivo,” will take place at 10:30 a.m. on Wednesday, Feb. 6, 2013, in the Pennsylvania Convention Center, Hall C. ABSTRACT: tinyurl.com/acw94xg Provided by American Institute of Physics

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Read more at: http://phys.org/news/2013-02-quantum-dots-vitamin-d-tumors.html#jCp

The nanomechanical signature of breast cancer


Using ARTIDIS to feel the tissue structure of a tumor biopsy by a nanometer-sized atomic force microscope tip. Image: Martin Oeggerli

 

 

 

 

 

 

Using ARTIDIS to feel the tissue structure of a tumor biopsy by a nanometer-sized atomic force microscope tip. Image: Martin Oeggerli

The spread of cancer cells from primary tumors to other parts of the body remains the leading cause of cancer-related deaths. The research groups of Roderick Lim and Cora-Ann Schoenenberger from the Biozentrum of the University of Basel, reveal in the journal Nature Nanotechnology how the unique nanomechanical properties of breast cancer cells are fundamental to the process of metastasis. The discovery of specific breast cancer “fingerprints” was made using breakthrough nanotechnology known as ARTIDIS. Lim’s team has now been awarded about 1.2 million Swiss francs from the Commission for Technology and Innovation (CTI) to further develop ARTIDIS.
Breast cancer is the most common form of cancer in women with 5,500 patients being diagnosed with the disease in Switzerland each year. Despite major scientific advancements in our understanding of the disease, breast cancer diagnostics remains slow and subjective. Here, the real danger lies in the lack of knowing whether metastasis, the spread of cancer, has already occurred. Nevertheless, important clues may be hidden in how metastasis is linked to specific structural alterations in both cancer cells and the surrounding extracellular matrix. This forms the motivation behind ARTIDIS (“Automated and Reliable Tissue Diagnostics”), which was conceived by Dr. med. Marko Loparic, Dr. Marija Plodinec and Prof. Roderick Lim to measure the local nanomechanical properties of tissue biopsies.

Fingerprintingbreast tumors
At the heart of ARTIDIS lies an ultra-sharp atomic force microscope tip of several nanometers in size that is used as a local mechanical probe to “feel” the cells and extracellular structures within a tumor biopsy. In this way, a nanomechanical “fingerprint” of the tissue is obtained by systematically acquiring tens of thousands of force measurements over an entire biopsy.

Subsequent analysis of over one hundred patient biopsies could confirm that the fingerprint of malignant breast tumors is markedly different as compared to healthy tissue and benign tumors. This was validated by histological analyses carried out by clinicians at the University Hospital Basel, which showed a complete agreement with ARTIDIS. Moreover, the same nanomechanical fingerprints were found in animal studies initiated at the Friedrich Miescher Institute.

Plodinec, first author of the study, explains: “This unique fingerprint reflects the heterogeneous make-up of malignant tissue whereas healthy tissue and benign tumors are more homogenous.” Strikingly, malignant tissue also featured a marked predominance of “soft” regions that is a characteristic of cancer cells and the altered microenvironment at the tumor core. The significance of these findings lies in reconciling the notion that soft cancer cells can more easily deform and “squeeze” through their surroundings. Indeed, the presence of the same type of “soft” phenotype in secondary lung tumors of mice reinforces the close correlation between the physical properties of cancer cells and their metastatic potential.

ARTIDIS in the clinics
“Resolving such basic scientific aspects of cancer further underscores the use of nanomechanical fingerprints as quantitative markers for cancer diagnostics with the potential to prognose metastasis,” states Loparic, who is project manager for ARTIDIS. On an important practical note, a complete biopsy analysis by ARTIDIS currently takes four hours in comparison to conventional diagnostics, which can take one week. Based on the potential societal impact of ARTIDIS to revolutionize breast cancer diagnostics, Lim’s team and the Swiss company Nanosurf AG have now been awarded about 1.2 million Swiss francs by the Commission for Technology and Innovation (CTI) to further develop ARTIDIS into a state-of-the-art device for disease diagnostics with further applications in nanomedicine.

Over the next two years, Lim and colleagues will engage and work closely with clinicians to develop ARTIDIS into an easy-to-use “push-button” application to fingerprint diseases across a wide range of biological tissues. As a historical starting point, the first ARTIDIS demo-lab has already been established at the University Hospital Eye Clinic to collect data on retinal diseases with the goal of improving treatment strategies.

The nanomechanical signature of breast cancer

Source: University of Basel