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Cancer therapy without side-effects?

Most of you know at least one person who has been affected by cancer and treated by chemotherapy, suffering from side-effects such as hair loss or nausea. This is because chemotherapy attacks both healthy and unhealthy cells in the whole body. Now, Australian researchers are using nanotechnology to offer chemotherapy relief. They've created 'nano-cells' from 'inert' bacteria -- meaning they can't reproduce -- which can deliver potent drugs exactly where they're needed. As this new therapy allows to target very precisely the tumors, the amounts of drugs are much smaller and the harmful side-effects of chemotherapy will be avoided in the future. This method could be used for a wide variety of cancers and human clinical trials should start by the end of this year.
Written by Roland Piquepaille, Inactive

Most of you know at least one person who has been affected by cancer and treated by chemotherapy, suffering from side-effects such as hair loss or nausea. This is because chemotherapy attacks both healthy and unhealthy cells in the whole body. Now, Australian researchers are using nanotechnology to offer chemotherapy relief. They've created 'nano-cells' from 'inert' bacteria -- meaning they can't reproduce -- which can deliver potent drugs exactly where they're needed. As this new therapy allows to target very precisely the tumors, the amounts of drugs are much smaller and the harmful side-effects of chemotherapy will be avoided in the future. This method could be used for a wide variety of cancers and human clinical trials should start by the end of this year.

Here are some short excerpts of the Agençe France-Presse report.

Researchers there have used bacterial cells stripped of reproductive powers to develop receptacles capable of carrying any chemotherapy drug. These 'nano-cells', which are about one-fifth the size of of normal human cells, are then tagged with antibodies, which are attracted to cancerous tumours. Once the nano-cell hits the cancer and attaches, the drug is released directly into the malignant growth.

As said Jennifer MacDiarmid of Sydney-based biotechnology company EnGeneIC, "Your hair wouldn't fall out, you wouldn't throw up... some chemotherapy is life-threatening in itself." And she added that with their new method, "There is no other system where you can get so much drug concentrated into a little parcel."

In "Cancer therapy cuts side effects," BBC News adds more details about the future of this method.

It is hoped the technique could treat tumours in the breast, ovaries, colon and lungs. So far it has been used in mice and dogs, and the researchers plan to begin human trials shortly. In tests, the technique reduced tumours in animals without side effects - and by using only a very small amount of drug. Dr MacDiarmid said the treatment could potentially be used on any solid tumours.

In "'Mini-cells' could stop side-effects of chemotherapy," New Scientist asks the question: "Could bacteria be the future of cancer therapy?" And it describes what the researchers have done with bacteria.

When bacteria divide, they normally do so at their centres. But Himanshu Brahmbhatt and Jennifer MacDiarmid, of EnGeneIC in Sydney, Australia, have found a way of forcing them to divide at their ends, producing small buds of cytoplasm each time. They have also discovered that a range of different drugs could be packaged into these particles. These "mini bacteria", or EnGeneIC Delivery Vehicles (EDVs) as the company has dubbed them, are cheap and easy to produce, and can be used as targeted drug delivery vehicles.
"They look like bacteria but they have no chromosomes and are non-living," says MacDiarmid. "And because they have a rigid membrane they don't break down when injected, so they carry their payload happily to the target site."

This research work has been published online by Cancer Cell under the name "Bacterially Derived 400 nm Particles for Encapsulation and Cancer Cell Targeting of Chemotherapeutics" (Volume 11, Issue 5, Pages 431-445, May 2007). Below is the beginning of the abstract.

Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility.

These findings have also recently been presented by Himanshu Brahmbhatt, Joint CEO, EnGeneIC Pty Ltd, at the RNAi 2007 conference held in Boston, Massachusetts, on May 3, 2007. By scrolling down through this page, you'll discover the abstract of the presentation named "Turning siRNA into a cancer therapeutic: Bacterially-derived non-living nanoparticles for the targeted delivery of siRNA and shRNA for potent anti-tumor effects in vivo." [Note: siRNA is a shortcut for Small interfering RNA, as described by Wikipedia.] Below is a comment about how these nanoparticles, dubbed as EDVs (EnGeneIC Delivery Vehicles), are acting.

We discovered that EDVs can be packaged with therapeutically significant concentrations of siRNAs as well as chemotherapeutic drugs of differing charge, hydrophobicity and solubility. Targeting of EDVs via bispecific antibodies (BsAbs) to receptors on cancer cell membranes results in endocytosis, intracellular degradation and release of the payload. Intact and fully functional siRNAs are released intracellularly to achieve target mRNA knockdown resulting in highly significant anti-tumor effects as well as drug resistance reversal.

And for even more information, you can read the patent granted to EnGeneIC Pty Ltd under the name "Intact minicells as vectors for DNA transfer and gene therapy in vitro and in vivo" about this new form of cancer therapy. Here are two links provided by the World Intellectual Property Organization (WIPO) and by FreePatentsOnline.com.

Sources: Agençe France-Presse, via COSMOS magazine, Australia, May 14, 2007; BBC News, May 11, 2007; Linda Geddes, New Scientist, May 7, 2007; and various websites

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