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Synergistic benefit of using nanotechnology to simultaneously deliver two anticancer agents

It is usually the case that nanostructures have useful properties because they are so small. In the case of drug delivery, nanoparticles are useful because they are large on a molecular scale. The National Cancer Institute’s Alliance for Nanotechnology in Cancer describes research from two different groups using two different types of nanoparticles. In each case the nanoparticles were large enough to deliver two different anticancer agents to cancer cells. Each group found that the combination delivery was more effective at killing cancer cells than if the drugs were delivered separately. “Nanoparticles Deliver One-Two Therapeutic Punch to Kill Tumor Cells“:

The standard approach to cancer therapy today is to mix and match chemotherapy drugs in order to attack tumors in multiple ways. Now, two separate teams of investigators have demonstrated that using nanoparticles to deliver multiple drugs simultaneously can produce a synergistic effect that boosts the cell-killing ability of both drugs.

In one study, a team of investigators at Northwestern University has shown that they can combine two powerful but extremely toxic anticancer agents – cisplatin and doxorubicin – in one polymer nanoparticle, producing a substantial boost in their ability of the combination to destroy tumors. In addition, the two-in-one nanoparticle reduces the amount of both drugs needed to kill cancer cells, which presumably would reduce the toxic side effects associated with these drugs.…

Though originally designed to carry arsenic trioxide to solid tumors, the nanoparticles used in this study are proving to be quite versatile in their ability to ferry a wide range of cargos to malignancies. In this study, the investigators wanted to see if delivering two drugs in one nanoparticle offered any advantages of delivering them without the nanoparticle or in separate nanoparticles. The nanoparticles, which the researchers call nanobins, are made by encasing a liposome inside a pH-responsive polymer cage. In this case, doxorubicin is entrapped within the liposome’s core, while cisplatin was entrapped in the polymer cage.

In an initial set of experiments, the investigators determined that a 5 to 1 ratio of cisplatin to doxorubicin was the most effective at treating ovarian tumors when the two drugs were combined in the same nanoparticle. When the two drugs were administered at this ratio but with each in its own nanoparticle, the combination was not only less effective at killing malignant cells, but the two drugs appeared to be interfering with each other, a phenomenon often observed in clinical practice. Administering the two drugs in the same nanoparticle ensures that the drugs are hitting their intracellular targets at the same time, which is what likely leads to the synergism observed in this study.

Meanwhile, Mansoor Amiji and Zhenfeng Duan, co-principle investigators of the Cancer Nanotechnology Platform Partnership at Northeastern University, have shown that a different type of polymer nanoparticle can also deliver two anticancer agents simultaneously and as a result can kill cancer cells that have become resistant to drug therapy. In this case, the researchers synthesized biocompatible polymer nanoparticles that entrapped paclitaxel and lonidamine and that targeted the epidermal growth factor receptor (EGFR) that is overexpressed on highly aggressive tumors. When added to tumor cells growing in culture, the nanoparticle containing both drugs was far more effective at killing the drug-resistance cells than when the two drugs were co-administered in separate nanoparticles.…

The demonstrated benefit of more complex and programmable behavior on the part of nanoparticles developed for drug delivery will perhaps drive the development of still more complex and programmable nanostructures, eventually leading to advanced nanotechnology based upon atomically precise manufacturing.

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