Greek mythology details the end of the 10-year war with Troy when the Greeks convinced the Trojans that their giant wooden horse was a peace offering. But soldiers were hidden in the belly of the horse and emerged at night after the Trojans brought the “gift” inside their city, leading to the decisive defeat of Troy.
Keep that in mind concerning the agreement recently announced by the University of North Texas Health Science Center and the French biopharmaceutical company Cerenis Therapeutics to develop HDL-based drug delivery systems for treating cardiovascular and metabolic diseases.
The strategic partnership will combine the expertise of the research team led by Andras Lacko, professor of physiology and anatomy at UNT Health Science Center, with the France-based company Cerenis Therapeutics, which has developed a treatment platform using artificial HDL.
The “HDL Drug Delivery Initiative” will focus on developing new strategies to address difficult-to treat-patients by creating a unique HDL platform technology for drug delivery, particularly in using that system to fight cancer.
HDL cholesterol is often referred to as good cholesterol.
“This friendly scavenger cruises the bloodstream,” says the website WebMD. “As it does, it removes harmful bad cholesterol from where it doesn’t belong.”
Lacko’s research has long focused on the use of nanoparticles to deliver anti-cancer drugs directly to tumors while avoiding damage to healthy cells to spare patients the side effects of chemotherapy.
“A number of laboratories, including ours, have shown that artificial HDL can carry drugs selectively to tumors and avoid most of the off-target sites,” Lacko said in an interview with the Fort Worth Business Press.
“We’ve been working at this for quite a while, and there’s a number other labs around the world actually working at it. We’ve been working at this probably the longest. We started in 1997, so it’s been 21 years since we’ve been doing this,” Lacko said.
In traditional chemotherapy, cancer-fighting drugs – which are toxic to the body – are carried in a solvent – also toxic to the body – and injected into the patient’s bloodstream. There are a number of serious side effects.
The actual cancer-fighting drugs last in the body for only a few hours before the body eliminates them, but the toxicity of the treatment itself limits how frequently chemotherapy can be done.
What is important is how long the anti-cancer drugs can stay in contact with the cancer cells.
“We don’t use any excipients [inert substances] or any solvent,” Lacko said. “The drug goes straight inside the HDL and it appears that higher doses could be used because the drug does not interact with normal tissues but primarily with the tumor.”
The process has not been tested in humans.
Lacko said the liver receives cholesterol from an HDL polar receptor called Scavenger Receptor Type B-1.
“It works out that most tumors have a very high level of expression of this receptor, which we discovered very early. This encouraged us to keep going because this provides a potentially tumor-selective delivery of the drug as long as it’s in the HDL,” he said.
It also turns out that cancer cells like HDL molecules.
“So this is a Trojan horse kind of model because the cancer cell thinks it’s going to get cholesterol but it’s actually getting poison,” Lacko said.
He stressed that the process, despite the long period of study, still has far to go.
Unknown, for example, is how long the cancer drug remains in the body at an effective therapeutic dosage.
“I can only guess because we haven’t done any studies,” Lacko said, “but the HDL has a very long circulation time. It’s several days. And the release of the drug would be slower – but the drug would stay in the circulation much longer.
“But once again, we anticipate that the drug would be protected from interacting with normal tissues and it would slowly attack the tumor because it will stay in the circulation longer inside the HDL,” he said.
Other companies are working on nanotechnology to treat cancer and other ailments, among them NanOlogy, based in Fort Worth, which is studying nanoparticles of cancer-fighting drugs injected directly into tumors.
HDL particles as biocompatible adaptive carriers loaded with active agents hold promise to target and selectively kill malignant cells while avoiding healthy ones. A wide variety of drugs can be embedded in these particles targeting markers specific to cancer cells and bring these potent drugs to their intended site of action, with lowered systemic toxicity.
Cerenis is delighted to work with Lacko and UNTHSC, said Jean-Louis Dasseux, CEO of Cerenis Therapeutics.
“This partnership will focus on innovative solutions for the HDL drug delivery market,” he said. “It is an important step forward for our technology development program and our nanotechnology platform as we look forward to building a strong integrated relationship beneficial for both parties.”
Cerenis developed the treatment platform originally as a way for the artificial HDL to remove plaque buildup in the body’s blood vessels.
Cerenis’s ongoing “TARGET” study is the first clinical study ever done testing the potential of labeled HDL to visualize tumors in cancer patients, the company said in a news release.
“89Zr-labeled HDL mimetic CER-001 will allow for non-invasive evaluation of the potential of drug delivery strategies in selected cancers,” the release said. “A number of preclinical studies have already validated the concept; however, this study will support the opportunity to treat cancer patients using HDL nanoparticles as a specific drug delivery platform targeting tumors.”
“I might point out that these HDL nanoparticles that they make are made from the same ingredients as HDL, but they are very, very small,” Lacko said. “They’re not quite as small as HDL, but they are smaller than most nanoparticles that are used in therapeutics.
“They are in the range of 15-20 nanometers, and that is on a very low range of nanoparticles,” he said. “This is very helpful because the tumor environment is highly disorganized and the smaller a particle is, the easier it’s going to be able to penetrate and get to the business end of the tumor.”
Lacko said his laboratory hasn’t done any experiments beyond mice and that’s not a very good model.
“We hope to expand our mouse model work now, as well as hopefully not too long from now, go to human studies,” he said.
“This partnership will focus on innovative solutions for the targeted drug delivery market. It is an important step forward for our technology development program and our nanotechnology platform as we look forward to building a strong integrated relationship beneficial for both parties,” Cerenis’s Dasseux said.
As part of the agreement, Lacko’s research group will conduct early preclinical research related to the development of new drug complexes based on HDL platforms.
“This work will include developing further understanding of the physical/chemical properties relevant to creating an HDL-based carrier, developing new strategies to trap biologically active molecules within HDL, optimizing the structure of HDL complexes and demonstrating the activity, efficacy and advantages of the HDL complexes in cell models,” a joint news release said.
This article includes material from UNTHSC writer Jan Jarvis and from news releases from both UNTHSC and Cerenis Therapeutics.