Release date: 2016-06-20
Scientists at Case Western Reserve University and the Massachusetts Institute of Technology found that when they encapsulated phenanthriplatin (hereinafter referred to as phenanthroline) in tobacco-to-the-box virus (tobaccomosaic virus) nanoscale particles After the application, not only the tumor of the triple-negative breast cancer in the mouse was reduced, but also the tumor was four times smaller than the traditional anticancer drug cisplatin or unencapsulated phenanthroline. This research was published in the ACS Nano journal of the American Chemical Society.
Platinum anticancer drugs have been widely used since the 1980s. When these drugs cross-link with cancer cell DNA, which in turn blocks DNA transcription, cancer cells die. More than half of cancer patients' chemotherapy relies on platinum compounds such as cisplatin and carboplatin, which is especially effective against testicular cancer. However, in view of the increasing resistance of cancer to cancer, scientists have been studying newer platinum compounds.
In 2012, Stephen J. Lippard, a professor of chemistry at the Massachusetts Institute of Technology, discovered that when he replaced a chlorine atom in cisplatin with phenanthridine, the new compound phenoplatin formed. (phenanthriplatin) is easier to enter cancer cells with high efficacy and low side effects. In experiments directed at tumor cells such as lung cancer, breast cancer, and bone cancer, phenanthroline showed 4-40 times the anticancer ability equivalent to cisplatin.
Professor Lipard's research encountered obstacles in the application of phenanthrene to model animals: the efficacy of phenanthroline injected into cancer-bearing mice is no different from traditional platinum compounds. He immediately realized that phenoplatin did not fully function, probably because it was consumed before it reached the cancer cells.
Professor Lipard, who explored the ideal drug delivery system, found the answer at Nicole Steinmetz, a bioengineering expert at Case Western Reserve University. The tobacco mosaic virus TMV studied by Steinmetz can be said to be the perfect carrier of phenanthrene: it is an elongated hollow cylindrical tube with a radius of 4 nm and a negative wall; the radius of phenanthroline is about 1 nm. The silver nitrate is positively charged after processing. The TMV virus does not infect normal human cells. The long strips allow the virus to hide at the edge of the blood vessels without being detected by immune cells, and traverse the vascular structure of the tumor and sneak into cancer cells.
Due to the high pH in the blood, TMV virions carrying toxic phenanthrene will not decompose until they reach the lysosomal compartments of cancer cells. The released phenanthroline binds to cancer cell DNA at a single site, hinders DNA transcription, causes apoptosis, and is more lethal than cisplatin that forms cross-linking with DNA.
The collaboration between Lipard and Steinmetz successfully demonstrated the superiority of TMV in carrying phenoplatin in mice with triple-negative breast cancer. They are still doing more related experiments, including studying other types of cancer, and how to process viral vectors to make them easier to accumulate after entering cancer cells.
Since platinum compounds were first approved for chemotherapy in 1978, they have caused enormous toxic side effects, including nausea, vomiting, deafness, nerve damage, liver toxicity, etc., while saving thousands of lives. The key to changing this status quo may exist in new platinum compounds and safer and more precise drug delivery systems.
Source: DeepTech Deep Technology
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