Our lymph nodes are the canaries within the coal mine of our immune system — firing into gear at the primary indication of illness, then sending immune cells where they’re needed within the body to fight infection and disease.
For the nearly 20 million patients all over the world diagnosed with cancer every year, the lymph nodes are a useful early indicator of whether their cancer has metastasized — when cancer cells begin to spread to a different organ. Catching metastasis as early as possible signifies that the patient may be administered the vital chemotherapy and immune therapies that may vastly improve their prognosis.
Researchers at USC’s Alfred E. Mann Department of Biomedical Engineering have developed a brand new nanoparticle that may “hitch a ride” on immune cells, or monocytes. Due to its tiny size, the particle can tag along directly into lymph nodes and help metastasis show up on MRIs where it could otherwise be too hard to detect. The outcomes could lead on to more advanced contrast agents that may be injected into patients to enhance MRI cancer screenings of the lymph nodes.
The work has been published in ACS Nano and was led by Eun Ji Chung, the Dr. Karl Jacob Jr. and Karl Jacob III Early-Profession Chair, and Noah Trac, a Ph.D. student within the Chung Lab.
While lymph nodes are an important think about cancer detection, screening them via biopsy is painful and invasive, and might result in unwanted unwanted effects like infection, lymphedema and thrombosis. Imaging tools corresponding to MRI detection are non-invasive. Still, additionally they have significant shortcomings in relation to screening lymph nodes,
“MRIs will have a look at the lymph node’s size, but that doesn’t have an incredible connection and correlation to the incontrovertible fact that it’s metastatic,” Chung said. “Even when you could have a chilly, your lymph nodes will start inflaming.”
“The most important issue with current MRI techniques isn’t that they do not detect the immune cells,” Trac said. “A serious issue with current contrast agents is that there isn’t a cancer-targeting mechanism, so most lymph nodes are lit up equally, no matter whether or not there may be cancer.”
To deal with this challenge, Chung, Trac and their co-authors developed a nanoparticle that targets a receptor present on each tumor cells and immune cell monocytes — cells that travel to the lymph nodes and are increasingly prevalent under disease conditions.
“The thought behind this nanoparticle is to try to direct the delivery of the gadolinium contrast agent to lymph nodes which have cancer, in order that they show up brighter on the MRI than healthy lymph nodes,” Trac said.
The diagnostic tool would also offer strong clinical value for doctors to not only catch first-time metastasis during an initial cancer diagnosis, but it’s going to also allow clinicians to maintain track of cancer reoccurrence.
“Just say a primary tumor has been removed, but perhaps they didn’t get all of it, or the cancer comes back and it’s metastatic for the second time. Recurrent metastasis is way harder to detect and might result in worse outcomes for the patient,” Chung said.
Hitching a ride to light up cancer
The nanoparticles work by targeting a protein expressed by cancer cells, referred to as C-C chemokine receptor 2 (CCR2). The particles “hitchhike” onto the immune cell monocytes that the body produces that also express this same receptor in response to the cancer. The monocytes then give the particles a free ride into the lymph nodes, where the particles can effectively highlight the metastatic cancer cells and enable clearer detection via MRI.
“The rationale why this mechanism works, along with the targeting elements, is because our particle size can also be very unique, and it could actually reach the lymph nodes,” Chung said. “We found there is a size cut-off and our particle type is in a position to pass into the lymph nodes and goal cancer cells which have gotten there, together with the monocytes that express this receptor.”
The method offers game-changing advantages for the early detection of cancer metastasis within the lymph nodes. While previously, metastasis could only be assessed by a rise in lymph node size; the brand new Chung Lab particles could lead on to MRI contrast agents that may highlight metastatic cells in lymph nodes which will otherwise appear normal. In experiments using a mouse model, the team demonstrated that the particles increased the signal detected by MRI by as much as 50%.
“The particles are amplifying the signal, and we are able to see that at points where the lymph nodes have not yet modified in size, and the metastasis could be very early. We’re providing this profit where, clinically, you would not give you the chance to see metastasis in any respect,” Chung said.
The following step for the research team is to get their work closer to clinical applications for MRI contrast agents. The work has been submitted to the Nanoparticle Characterization Laboratory on the National Institutes of Health, where a 3rd party will assess and validate the work to enable it to maneuver closer to human trials.
