Nano Ghost Busters

Special delivery to combat cancer

Prof. Marcelle Machluf, Deputy Executive Vice President for Research for the Pre-Clinical Research Authority of the Technion

The ultimate goal in cancer therapy is a "magic bullet" that provides a versatile delivery platform for site‐specific targeting of multiple compartments of the cancer tissue. Prof. Marcelle Machluf, of the Faculty of Biotechnology and Food Engineering, is leading the way with her novel drug delivery system, using the "nanoghost" as a vehicle to transport the therapeutic to the target cells in a nontoxic manner.

In the Laboratory for Cancer Drug Delivery and Cell Based Technologies, nanoghosts are produced from the cell membranes of naturally targeted mesenchymal stem cells. Nanoghosts can be loaded with different drugs or genes and retain the selective targeting capabilities of their source cells while leading to tumor growth inhibition. This innovative technology dramatically increases the therapy’s efficacy and prevents the side effects associated with existing chemotherapy. Recently, the nanoghost therapy has been proven also as a gene delivery platform to combat cancer.

The clinical application of gene therapy for cancer is still very limited. The prevalent method, which inserts genes into target cells using viruses, may arouse a harsh immune response and still cannot reach the clinical setting.

An article published in February 2016 in Nano Letters heralds a breakthrough in the accurate delivery of genes to the target without the use of viruses. Here, Machluf's team report on nanoghosts, loaded with genetic material, that are injected directly into the bloodstream through which they navigate to the tumor. The tumor cells begin to produce an anti-cancer protein only once they reach the target - bypassing healthy tissue en route. The anti-cancer protein affects not only the target cells, but also the adjacent cancer cells and the essential blood vessels that support the tumor.

“The difficulty of delivering agents to the brain represents a major impediment to improving outcomes in patients suffering from brain tumors.”

Furthermore, since these vehicles do not generate any immune response, there is no requirement to harvest the mesenchymal stem cells from the individual patient.

Animal models have yielded very encouraging data: the mechanism works, doubling life expectancy after the development of prostate cancer, leading to a delay of over 75 percent in the development of prostate cancer, and of over 50 percent in the case of non-small cell lung carcinoma.

Electron microscopy image of nanoghosts loaded with nucleic acids

In a new research project, Machluf teams up with Assoc. Prof. Eva Hernando-Monge at NYU Langone Medical Center to investigate the possibility of suppressing melanoma - skin cancer that has spread or metastasized to the brain, and is often incurable - using a novel drug delivery system to the brain.

According to Machluf, “In this study we are checking the possibility of loading nanoghosts with anticancer drugs or molecules that inhibit the expression of protein necessary for tumor cell growth and injecting them into the bloodstream. The drugs will be able to cross the blood-brain barrier, detect the brain tumor, and attack it directly. We need to complete the preclinical trials and examine the impact of this technology on humans.”

This latest study is one of the first two joint projects in the Langone-Technion oncology research program, supported by noted philanthropists and NYU Langone Trustees Laura and Isaac Perlmutter.

“The drugs will be able to cross the blood-brain barrier, detect the brain tumor, and attack it directly.”

“Our studies should provide important information on nanoghosts’ general value as drug and gene carriers or gene silencing molecules to the brain, and create potential for new treatment approaches against brain tumors and metastases,” says Machluf. “The difficulty of delivering agents to the brain represents a major impediment to improving outcomes in patients suffering from brain tumors. Our state-of-the-art nanovehicle promises safer, simpler, and more clinically relevant treatments than existing vehicles, which are comprised of polymers or synthetic vesicles which largely lack the ability to enter the brain and to target evolving and changing pathologies.”

Machluf is an affiliated member of the Technion Integrated Cancer Center in the Rappaport Faculty of Medicine. In 2014, Machluf was named recipient of the Juludan Prize, awarded for outstanding research projects with applications directly geared to medicine. In 2015, she was appointed Deputy Executive Vice President for Research for the Pre-Clinical Research Authority of the Technion.