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The first drug-loaded nanoparticle approved to treat cancer is in line for an upgrade. Researchers at Northeastern University have improved the tumor-killing activity of liposomal doxorubicin, known as Doxil™, by attaching a monoclonal antibody that recognizes a protein found on the surface of cancer cells. The resulting targeted liposome improves drug uptake by malignant cells and, more importantly, increases the potency of the original liposome by as much as eightfold. This work is reported in the European Journal of Pharmaceutical Sciences.
To target liposomal doxorubicin, Vladimir Torchilin, Ph.D., and former graduate student Tamer Elbayoumi, Ph.D., used a monoclonal antibody discovered a decade ago by Torchilin and his colleagues. This antibody binds to a protein found in nucleosomes, a protein-DNA construct that organizes the chromosomes of all multicellular organisms, including humans. In healthy cells, nucleosomes are found only in the cell nucleus, but a broad variety of cancer cells contain a receptor on the cell membrane that recognizes nucleosomes. This particular monoclonal antibody, named mAb 2C5, recognizes and binds to that same receptor, while showing no propensity to bind to healthy cells. Each modified liposome contains approximately 70 to 80 surface-attached monoclonal antibodies.
Tests using a wide range of cultured tumor cells showed that mAb 2C5-targeted liposomal doxorubicin bound avidly to the cells. More importantly, uptake by those cells was rapid, far faster than with untargeted Doxil™ or Doxil™ modified with a control antibody that does not recognize tumor cells. Similarly, the targeted formulation was far more toxic toward all seven tumor cell lines tested, as it was in one preliminary in vivo study using a mouse xenograft model of human cancer. In addition, the investigators found that the targeted formulation, but not plain Doxil™, was also effective at killing a colon cancer cell line that is normally resistant to both Doxil™ and free doxorubicin.
This work is detailed in the paper "Enhanced cytotoxicity of monoclonal anticancer antibody 2C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines." An abstract of this paper is available through PubMed.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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