Nanoparticles “hitchhike” on immune cells to detect cancer metastases early

Lymph nodes are the canaries in the coal mine of our immune system: They kick in at the first sign of illness, then send immune cells to where they’re needed in the body to fight infections and disease.

For the nearly 20 million patients worldwide who are diagnosed with cancer each year, lymph nodes provide a valuable early indicator of whether their cancer has metastasized—that is, when cancer cells begin to spread to another organ. Detecting metastases as early as possible means the patient can receive the necessary chemotherapy and immune therapies that will significantly improve their prognosis.

Researchers in USC’s Alfred E. Mann Department of Biomedical Engineering have developed a new nanoparticle that can “hitch a ride” on immune cells, or monocytes. Because of its small size, the particle can slip directly into lymph nodes and help metastases show up on MRI scans where they would otherwise be too difficult to detect. The findings could lead to more advanced contrast agents that can be injected into patients to improve lymph node cancer screening using MRI.

The work was published in ACS Nano and was led by Dr. Karl Jacob Jr. and Karl Jacob III Early Career Chair, Eun Ji Chung, and Noah Trac, Ph.D. student in the Chung laboratory.

Although lymph nodes are a critical factor in cancer detection, screening for them by biopsy is painful and invasive and can lead to unwanted side effects like infection, lymphedema, and thrombosis. Imaging tools such as MRI detection are non-invasive. However, they also have significant gaps in lymph node screening,

“MRI scans will look at the size of the lymph node, but that has no connection or correlation to whether it is metastatic,” Chung said. “Even if you have a cold, your lymph nodes will start to become inflamed.”

“The major problem with current MRI techniques is not that they don’t detect immune cells,” Trac said. “A major problem with current contrast agents is that there is no cancer-targeting mechanism, so most lymph nodes are illuminated the same whether there is cancer or not.”

To address this challenge, Chung, Trac and their co-authors developed a nanoparticle that targets a receptor present on both tumor cells and immune cell monocytes, cells that travel to lymph nodes and become more increasingly prevalent in pathological conditions.

“The idea behind this nanoparticle is to try to direct the delivery of the contrast agent gadolinium to lymph nodes with cancer, so that they appear brighter on MRI than healthy lymph nodes.” , Trac said.

The diagnostic tool would also provide strong clinical value to doctors, not only for detecting early metastases during an initial cancer diagnosis, but it would also allow clinicians to track cancer recurrence.

“Just say a primary tumor was removed, but maybe they didn’t get it all back, or the cancer comes back and is metastatic for the second time. Recurrent metastases are much harder to detect and can lead to worse patient outcomes,” Chung said.

Hitchhiking to shine a light on cancer

The nanoparticles work by targeting a protein expressed by cancer cells, known as CC chemokine receptor 2 (CCR2). The particles “hitchhike” on the monocytes of immune cells that the body produces and which also express this same receptor in response to cancer. The monocytes then allow the particles to flow freely into the lymph nodes, where the particles can effectively highlight metastatic cancer cells and allow for clearer detection via MRI.

“The reason this mechanism works, in addition to the targeting elements, is that the size of our particles is also very unique and they can reach the lymph nodes,” Chung said. “We found that there is a size limit and that our type of particle is able to pass into the lymph nodes and target the cancer cells that have gotten there, as well as the monocytes that express this receptor.”

The process offers revolutionary benefits for early detection of cancer metastases in lymph nodes. Whereas previously, metastases could only be assessed by an increase in lymph node size; Chung Lab’s new particles could lead to MRI contrast agents capable of highlighting metastatic cells in lymph nodes that might otherwise appear normal. In experiments using a mouse model, the team demonstrated that the particles increased the signal detected by MRI by up to 50%.

“The particles amplify the signal, and we can see this in places where the lymph nodes have not yet changed size and metastases are very early. We offer this advantage where, clinically, you might not see metastases ” Chung said.

The next step for the research team is to bring their work closer to clinical applications of MRI contrast agents. The work has been submitted to the National Institutes of Health’s Nanoparticle Characterization Laboratory, where a third party will evaluate and validate the work to bring it closer to human testing.