Scientists develop cancer therapy that reduces toxic chemotherapy effects

By Al Saint Jacques, MDLinx
Published November 14, 2016

Key Takeaways

Using gold nanoparticles to deliver a commonly used chemotherapy drug directly to the tumor, scientists from Virginia Tech and CytImmune Sciences were able to provide an effective treatment that also dramatically reduces side effects including hair loss, nausea, and nerve pain, according to a study recently published in the scientific journal Bioconjugate Chemistry.

Earlier this year, CytImmune Sciences asked David Kingston, a University Distinguished Professor of Chemistry with the Virginia Tech College of Science, to create a paclitaxel derivative that binds to gold-based nanoparticles while in the blood stream, only releasing the drug once it’s inside a cancerous tumor. Paclitaxel chemotherapy is widely used to treat breast, ovarian, lung, and colon cancer.

“Paclitaxel side effects occur because the drug is given intravenously and thus is distributed throughout the body, and not just to the tumor,” said Kingston, who joined the Virginia Tech Department of Chemistry in 1971. “In addition, the solvent used to allow infusion has its own toxicity. Paclitaxel could be a much more effective drug if it could be targeted directly to the tumor. This would allow each dose to be given without causing significant side effects, and would thus increase the potential for cures.”

In describing the benefits of the new approach, Kingston compared the traditional delivery of paclitaxel to using a shotgun with pellets. The blast of killing a tumor results in great collateral damage. Kingston and his team say their delivery method is like a finely tuned rifle, using CytImmune’s gold-based nanoparticles as the delivery bullet.

The gold nanoparticles are coated with both paclitaxel and tumor necrosis factor – a cell-signaling protein commonly called TNF. Gold nanoparticles are known to cling around cancerous tumors. TNF thus binds to the tumor blood vessel cells, ultimately killing them and reducing the high pressure inside the tumor, which prevents paclitaxel from reaching the cancer cells to kill them.

Using this new approach, the slowly released paclitaxel that is bound to the gold nanoparticles can reach the targeted cancer cells to kill them.

The researchers found that in early lab tests in treating mouse melanoma, a 2.5 milligram dose of paclitaxel delivered on Kingston’s gold nanoparticles vehicle was essentially as effective as a dose of 40 milligrams of paclitaxel by itself.

The delivery method is expected to soon move toward clinical trial, said Kingston.

In addition to Kingston, other members of his team included Jielu Zhao, a 2016 doctoral graduate in chemistry, now a chemist at Proctor and Gamble, and Shugeng Cao, a former post-doctorate researcher also in chemistry, now an associate professor at the University of Hawaii at Hilo.

Zhao and Cao carried out the actual synthesis of the paclitaxel derivatives with the designed linkers to allow them to bond to the gold nanoparticles, with Kingston supervising.

“This approach has the potential to be a game-changer in nanoparticle-based drug delivery systems,” said Kingston, “since it combines the power of drug targeting by tumor necrosis factor, with the advantages of nanoparticle delivery, including the low toxicity of nanoparticle drugs to normal, healthy tissue.”

“By combining the tumor blood vessel destroying activity of TNF with the cancer killing effect of paclitaxel onto CytImmune’s tumor-targeted, ‘stealth’ gold nanoparticles, Dr. Kingston’s team and CytImmune’s team may have potentially created a new cancer drug that is far more effective and less toxic to the human body,” said Lawrence Tamarkin, chief executive officer at CytImmune.

Work on the new drug was split between Virginia Tech’s main Blacksburg campus and CytImmune’s Rockville, Maryland, headquarters. Kingston has teamed up with CytImmune in the past on tumor-targeting nanomedicine.

Virginia Tech previously has used gold nanoparticles in unrelated anti-cancer research, including the Virginia-Maryland College of Veterinary Medicine which in experiments used gold nanoparticles to collect around tumors found inside a dog, and then utilized a non-ablative laser to target the gold nanoparticles, and thus the tumors. In essence, the veterinary approach killed cancer cells by heating them, versus Kingston’s approach directly targeting paclitaxel to tumors via the gold nanoparticles.

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