Spongelike Particles Show Promise for Delivering Drugs to Tumors

By Jim Stallard,

Pictured: Jan Grimm
Summary

Memorial Sloan Kettering researchers are investigating the use of tiny particles that behave like sponges to take in drugs and deliver them to tumors.

Memorial Sloan Kettering researchers have shown that tiny particles can be manipulated to act like sponges, taking in drugs and ferrying them to tumors. The minuscule objects hold on to their cargo with weak electric bonds, which give way as they draw near cancer cells.

The research, conducted in the laboratory of radiologist and molecular imaging specialist Jan Grimm, suggests that these spongelike nanoparticles, which the scientists dubbed nanophores, could deliver chemotherapy and other drugs more efficiently than current methods by ensuring they accumulate at the tumor site.

The researchers employed a particle called ferumoxytol, a drug already used clinically to treat patients with iron deficiency. Cancer drugs loaded onto ferumoxytol are held by the particle until the nanophore senses a slight drop in pH level, which signals a rise in acidity — one of the hallmarks of cancer cells.

“Having the tumor microenvironment and the cancer cells’ unique metabolism trigger the drug’s release is one thing that makes this approach novel,” says Charalambos Kaittanis, the study’s first author. “Until now, researchers have used nanoparticles that release the drug only when they are taken up by the cancer cells, or when the cells secrete certain enzymes. Nobody had tested whether the drug release could be caused by the tumor’s mildly acidic conditions.”

Another novelty of the method is that it allows the monitoring of drug delivery directly in a living organism. The use of magnetic resonance imaging (MRI) enables researchers to detect and measure the amount of drug loaded into the nanophore, as well as to confirm when it is released upon reaching its target.

The research was reported online March 4 in Nature Communications.

A Better Transporter

Although a variety of nanoparticles have been investigated as drug transporters, ferumoxytol offers some critical advantages. It already has been proven safe for use in humans, and unlike many nanoparticles, it does not need to be linked chemically to the drug it is carrying — a process that can alter a drug’s properties and reduce its effectiveness. In addition, ferumoxytol allows unambiguous proof that the drug is actually delivered.

“Although others have used MRI to visualize drug release, it was done somewhat indirectly using an imaging agent that was loaded onto the nanoparticle along with the drug,” Dr. Grimm says. “So what you were seeing was the imaging agent being released, and you had to assume the drug was going with it. You never knew for certain that the drug was not still trapped inside the nanoparticle.”

The researchers loaded the ferumoxytol nanophores with two chemotherapy drugs and tested them on human prostate cancer cells, both in a lab dish and in mice. Using MRI, they confirmed that the drugs were delivered to the target cells more efficiently when loaded onto ferumoxytol than if they were given on their own. In the animals, the drug-loaded nanophores shrank tumors markedly while the free drug just slowed their growth.

“We wanted to see if these particles could deliver two drugs simultaneously so they could be used for combination therapy, which has been shown to prevent resistance and maximize response,” Dr. Grimm says. “This approach mainly has proved effective in the treatment of prostate cancer, but it is increasingly considered for other cancers as well.”

The researchers repeated their experiments with human breast cancer cells implanted in mice — although a single drug was loaded in this case — with the same promising result.

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Noninvasive Imaging Potential

The nanophore method also could be used to improve noninvasive imaging of tissues, including lymph nodes that cancer often spreads to from a tumor. In January, Dr. Grimm’s laboratory reported in Nature Communications that ferumoxytol loaded with a radioactive tracer could show the location of lymph nodes where prostate cancer first spread in a mouse model for the disease. When imaged with positron emission tomography combined with MRI, the particles showed these nodes in great detail.

“This information could help surgeons who are sampling nodes or removing them completely — the imaging could pick up nodes they might otherwise have missed,” Dr. Grimm says.

The researchers believe ferumoxytol’s well-established safety profile in humans could speed its transition into clinical use.

“We’re at the beginning stages, but there’s great potential because of our ability to put multiple drugs in one nanophore,” Dr. Kaittanis says. “By learning more about the biology of the cancers, we think we can optimize the therapy by adjusting how much of each drug is delivered and tailoring it for individual patients.”

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Comments

Arecyou treating patients in clinical trials? Are you collaborating with physicians in other states.

Thank you.

James, the technology described in this story is still at the experimental stage and is not in clinical trials. Thank you for your comment.

I would like to have a post doc training on nanomaterials as drug delivery system. Are you accepting trainee in your lab? I am from the Philippines. Thank you.

I had full prostate removal and one lymph node of eleven found with Cancer. I was Gleason 3+4=7/10 & T-3bN1. Now four years later I am at .13 PSA from zero. Do you do the PSMA studies like UCLA and I understand the PSMA is approved in Germany. Have the detection levels for this test improved for PSA below .2 or at what levels are needed in USA or abroad such as Germany. Also not sure who all does PSMA around country. Any thoughts on what I should do in exploring options that are available or in test mode. I understand at UCLA it costs $2400 and not covered by Insurance but that is fine by me. Any advice would be helpful input as I search for Doctors to meet with. Currently in Seattle at Seattle Cancer Care Alliance.

Dear Gary, we currently have trials underway evaluating the use of PSMA. If you are interested in making an appointment for a consultation to learn more, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.

Please let me know whether PSMA therapy at MSK Cancer Center is in Clinical Trial stage (if yes, at what phase? still recruiting new patients?) or already approved for treating patients? Thank you very much in advance for your assistance.

MSK does not currently have any trials open that use this approach. If you are interested in making an appointment to find out what other treatment options may be available to you, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment and best wishes to you.

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