Polymer-coated nanoparticles carrying therapeutic drugs are showing great potential in cancer treatment, particularly for ovarian cancer. These nanoparticles can be engineered to home in on tumors, delivering their drug payload directly while minimizing the harmful side effects of traditional chemotherapy.

Over the past decade, MIT Institute Professor Paula Hammond and her team have developed various nanoparticles using a method called layer-by-layer (LbL) assembly. In animal studies, these particles have proven effective at targeting and treating tumors.

To make the leap from lab to clinic, the team has now introduced a new manufacturing technique that allows them to produce these nanoparticles much more efficiently and in significantly larger quantities.

“There’s a lot of promise with the nanoparticle systems we’ve been developing,” says Hammond, who also serves as MIT’s vice provost for faculty and is a member of the Koch Institute for Integrative Cancer Research. “We’ve seen very encouraging results, particularly in ovarian cancer models, and now our focus is on scaling this technology so it can be manufactured at a clinical level.”

The study, published in Advanced Functional Materials, was led by senior authors Hammond and Darrell Irvine, a professor of immunology and microbiology at the Scripps Research Institute. Ivan Pires PhD ’24 (now a postdoctoral researcher at Brigham and Women’s Hospital and a visiting scientist at the Koch Institute), Ezra Gordon ’24, and MIT research technician Heikyung Suh are also credited as authors.

A More Efficient Production Process

Hammond’s lab pioneered the LbL approach over ten years ago, enabling the precise assembly of nanoparticles by alternating layers of positively and negatively charged polymers. These layers can be customized with drugs and targeting molecules to enhance their cancer-fighting capabilities.

However, the original process was slow and labor-intensive, requiring a purification step after each layer using centrifugation. Later, the team adopted a faster method using tangential flow filtration, but it still didn’t support large-scale production.

“Even with tangential flow filtration, the process was limited to small batches,” Hammond explains. “Clinical trials demand a much larger, more scalable manufacturing solution.”

To overcome this, the researchers developed a microfluidic mixing system that assembles nanoparticles continuously as they move through microchannels. Each layer is added precisely, removing the need for purification after each step. This drastically reduces time and eliminates manual handling errors.

“Separation steps are often the most time-consuming and expensive part of the process,” Hammond says. “This new method streamlines production and aligns with FDA good manufacturing practice (GMP) standards.”

The microfluidic device used is already established in GMP manufacturing for other nanoparticle-based therapies like mRNA vaccines, making it well-suited for clinical translation.

“This approach minimizes human error and can be easily adapted to GMP-compliant production,” adds Pires. “It means we can develop innovations in nanoparticle design and quickly move them toward clinical trials.”

Toward Clinical Trials

With this new method, the researchers can produce 15 milligrams of nanoparticles—enough for around 50 doses—in just a few minutes, a process that previously took nearly an hour.

“To scale production, we simply continue running the chip,” says Pires. “It’s a much more efficient and scalable system.”

To validate the method, the team manufactured nanoparticles carrying interleukin-12 (IL-12), a cytokine previously shown by Hammond’s group to stimulate immune responses and reduce tumor growth in mice. The newly produced particles matched the effectiveness of earlier versions and demonstrated a unique mechanism: they attach to cancer cells without entering them, serving as immune-activating beacons within the tumor environment. In mouse models of ovarian cancer, this approach has delayed tumor progression and even led to cures.

The team has filed a patent and is working with MIT’s Deshpande Center to explore commercialization opportunities, including forming a startup. While the initial focus is on abdominal cancers like ovarian cancer, the platform has potential applications in other cancers, such as glioblastoma.

This work was supported by the U.S. National Institutes of Health, the Marble Center for Nanomedicine, the Deshpande Center for Technological Innovation, and the Koch Institute Support Grant from the National Cancer Institute.

Source: https://news.mit.edu/2025/engineers-develop-mass-manufacture-nanoparticles-drug-delivery-cancer-tumors-0403