Nanodrug fights breast cancer from the inside without healthy tissue damage

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With several medications a Nanodrug "Transport Vehicle" closely associated is possible breast cancer cells from the domestic and tumors grow target attack specific molecules that help to disseminate, without healthy cells intact, according to researchers at Cedars-Sinai Maxine Dunitz neurosurgical Institute in Los AngelesKalifornien.

In contrast to other drugs, the cancer cells from the outside, often with minimal effect, with laboratory mice, as the target of the Cedars-Sinai researchers showed that the Nanodrug that they have developed, belongs to a new class named Nanobiopolymeric conjugate or Nanoconjugates, can certain tumor-targeting chemicals to accumulate in tumor cells and beat mechanisms within the most demanding breast cancer cells.

Previous work with Nanoconjugates in the Cedars-Sinai has shown that a similar approach also in the attack on malignant brain tumors works.

Dr. Julia Y of Ljubimova, senior author of an article about the work in a recent issue of cancer research, said the press improve the many ways that Nanobiopolymers cancer cell targeting and treatment:

"Specific antibodies can be installed exactly the target proteins in tumor cells;" Resistance and systemic side effects are reduced because drugs are "bound to the platform and delivered inside the cancer cells without healthy cells; "and several drugs on a single platform, making it possible to simultaneously attack several targets, can be performed", said Ljubimova that laboratory in the Department of neurosurgery at Cedars-Sinai is the drug delivery and nanomedicine.

The researchers conducted a number of studies with laboratory mice, to show that this is very goal-oriented approach, using a combination of drugs, more effective than current standard of care.

The researchers targeted in their latest work on breast cancer HER2 positive breast cancer. In this type of breast cancer, women have more HER2 receptors on the surface of cancer cells carry a mutated form of a gene that to grow faster than other types of breast cancer.

HER2 positive breast cancer tends to be more aggressive and less on treatment response. The antitumor drug Herceptin (trastuzumab generic name) can sometimes help, but it carries risks than benefits.

Herceptin works by binding to the HER2 receptors on the surface of cancer cells and it stops signaling to grow the cell and parts; It also allows immune system killer cells to attach themselves when bound to the receptor and kill the tumor cells.

However, the efficacy of Herceptin is thus limited, that become resistant to 66 to 88% of patients, the tumours within 12 months of treatment. It may violate normal organs which it comes in contact with the researchers said.

The hope is that new drug technology are based on Nano polymer some of these problems overcome and offer a great potential in cancer therapy.

In their most recent cancer research paper Ljubimova and colleagues describe how she implanted their Polymalic acid (PMLA) Nanobiopolymer in mice with human breast cancer cells tested and found the drugs in cancer cells accumulated and significantly reduced tumor growth.

The PMLA, Nanoplatform, which refer to them as "biodegradable, non-toxic and nonimmunogenic", has a range of molecules such as Herceptin, each with a unique role. The Herceptin is aimed at existing HER2 protein, a different molecule depends on the genetic mechanism that triggers new protein, and a third molecule caused to open tumor blood vessels and allow the Nanodrug transporter to the cancer cell and release its payload.

"Different still were covalently to PMLA, including a combination of Morpholino antisense oligonucleotides (AON) from synthesis, directed against HER2/neu mRNA new HER2/neu receptor;" Trastuzumab (Herceptin), block bound anti-HER2/neu antibody breast cancer cells as a target and at the same time receptor activity inhibit; and Transferrin-receptor monoclonal antibody, the tumor vasculature and provide delivery of the Nanobiopolymer by the host system endothelial, your "the authors write."

An important feature of Nanoconjugates is the close chemical bonds that prevent the active drug components damaged or separately in tissues or in the blood that, as they their way to finding the tumor.

Another important characteristic, a result of the innovative drug engineering, is that the drugs are not active until they are in tumor cells. This ultimate assault is a well choreographed cascade of biochemical events that begins with homing on tumor cells, through the blood vessels and cell walls, release of antitumor drugs in the right place and at the right time, and then the mechanisms that help the blood vessels remove-feed the tumor cells.

Ljubimova said that their studies show their Nanobioconjugate is safe and efficient and can be adapted to handle a number of diseases.

"It is harmless normal tissue degraded to carbon dioxide and water, non-toxic, and, unlike some drugs, it is not immunogenic, meaning that it does not encourage desImmunsystems to towards the causes allergic reactions, the rich kannLebens-threatening symptoms sudden of mild cough or skin rashes to", "she added."

Ljubimova and two colleagues have declared a financial interest in a company researchers, which has a stake in this technology.

Medium for the current study the Winnick Family Foundation and the Department of neurosurgery at the Cedars-Sinai came Medical Center by the national institutes of health.

Support for future studies on the Nanoconjugate in the Cedars-Sinai nanomedicine research laboratory includes a five-year grant of the National Cancer Institute as part of nanotechnology in cancer program.

"Polymalic acid-based Nanobiopolymer provides efficient systemic treatment of breast cancer by inhibiting the HER2/neu receptor synthesis and activity."
Satoshi Inoue, Hui Ding, Jose Portilla Arias, Jinwei Hu, bindu Konda, Manabu Fujita, Andres Espinoza, sonal Suhane, Marisa Riley, Marcus gates, Rameshwar Patil, Manuel L. Penichet, Alexander V. Ljubimov, Keith L. Black, Eggehard holler and Julia y. Ljubimova.
Cancer RES 15 February 2011 71: 1454-1464
DOI:10.1158/0008-5472.CAN-10-3093

Additional source: Cedars-Sinai Medical Center (29 Mar 2011).

Posted by: Catharine paddock, PhD

See drug information on Herceptin.
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