Nanoparticle probes with surface enhanced Raman spectroscopic tags for cellular cancer targeting

November 24, 2015

Now they have a new tool - silver nanoparticles, embedded in nanoscale silica spheres, which can create cellular markers with a wide variety of colors that can be observed under the microscope. These nanoscale tags could provide a boost to high-throughput drug screening efforts.

Reporting its work in the journal Analytical Chemistry, a research team headed by Yoon-Sik Lee, Ph.D., developed their nanoparticle probes to be used in conjunction with Raman spectroscopy, a technique well-suited to high-throughput assays. Though other groups have developed nanoparticle-based Raman probes, those that use single nanoparticles do not produce an easily readable optical signal. The solution that Lee and his colleagues developed was to embed multiple silver nanodots and special dye molecules on the surface of silica spheres. The silver nanodots interact electronically with the dye molecules to produce a bright optical signal in a Raman spectrometer.

The researchers also developed methods for attaching cell-targeting molecules, such as antibodies, to the outside of the silica spheres without interfering with the optical properties of the final nanoparticle. In the work reported in this paper, the researchers used antibodies that target the HER2 receptor on breast cancer cells. Experiments showed that the targeted nanodots did bind to breast cancer cells with the HER2 receptor and were easily spotted using Raman spectroscopy.

This work is detailed is a paper titled, "Nanoparticle probes with surface enhanced Raman spectroscopic tags for cellular cancer targeting." An abstract of this paper is available through PubMed. View abstract.

nanoncer

Having discovered the role played by polyamine oxidation, the researchers with the help of their collaborators at Wayne State University, Detroit, MI, USA, synthesised a molecule called MDL 72,527 (MDL), which was previously known to be an inhibitor of acetyl polyamine oxidase (APAO). APAO catalyses the oxidation of acetyl polyamines produced by SSAT ? the process that results in the generation of ROS. MDL can, therefore, block androgen-induced ROS production in prostate cancer cells.

They injected MDL into the genetically engineered mice and found that it inhibited polyamine oxidation and reduced oxidative stress in the prostate glands of the animals. The treatment significantly increased overall survival and delayed time to prostate tumour development. In repeat experiments, between 50-60% of mice treated with MDL survived ten to twelve weeks longer than the untreated control group.

"To the best of our knowledge, this is the first report of a specific enzyme inhibitor MDL that blocks androgen-induced oxidative stress in the prostate and prevents spontaneous prostate tumour development," said Dr Basu.

More tests have to be carried out, but the researchers, working with the world-renowned prostate cancer clinician Dr George Wilding (a co-author of the paper), hope that phase I clinical trials of MDL might be able to start in 12-18 months.

Dr Basu said: "After surgery and radiotherapy for the primary tumour, breast cancer patients can be treated with several drugs such as tamoxifen and aromatase inhibitors that prevent or delay breast cancer recurrence. No such treatment exists for prostate cancer patients. After treatment of their primary tumours, prostate cancer in men is managed by watchful observation only. The immediate goal of our research is to develop agents such as MDL to fill this unmet medical need. If MDL, or any of the other agents that we are working with, can be expanded further to treat all high-risk men, we will be delighted."

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