PHOTO: COURTESY OF JAN-GEORG ROSENBOOM
Other current approaches such as injecting therapies directly into tumors often fail. Because the drugs may quickly spread elsewhere and are not visible with imaging technology, clinicians haven’t been able to track whether they’ve successfully delivered therapies to their intended target—until now.
Jan-Georg Rosenboom, a chemical engineer and visiting scientist and former senior postdoctoral researcher in the labs of Institute Professor Robert S. Langer ScD ’74 and Giovanni Traverso MD, MBBCh, is part of a team of MIT researchers pioneering a promising solution to these challenges: a gel-based drug delivery system called ImmunoGel that allows clinicians to inject a therapy once instead of multiple times and to control its extended release to target cancer tumors. ImmunoGel allows interventional radiologists to confirm drug delivery to its target using CT scan or ultrasound.
A preliminary study of mice with colon and breast cancer suggests that this new type of hydrogel also appears to activate and train the body’s immune system to fight new tumors, making it a potentially effective treatment for metastatic disease. This gel-delivered, FDA-approved immunotherapy led to tumor regression and improved survival. “Vaccinating your body against your own tumor is a fascinating paradigm, and there’s lots of people and new companies working on it, but rarely anybody thinks about correct delivery,” Rosenboom says.
ImmunoGel could safely and effectively carry a variety of drug types beyond cancer therapies, says Rosenboom, and the team is working with industry partners toward that goal. Traverso, the Karl Van Tassel Career Development Professor of mechanical engineering and a gastroenterologist at Boston’s Brigham and Women’s Hospital, said the gel-based treatment could be available in the next two to five years.
The power of polymers
Biocompatible (safe for living tissue) hydrogels are used for healing wounds such as burns; treating skin conditions, including eczema; and protecting healthy tissue during radiation treatment. Researchers worldwide are now exploring hydrogels for a range of additional functions including tissue regeneration and augmentation, engineering tumor models, boosting the body’s immune system, and slowing tumor regrowth after surgery.
Rosenboom’s pioneering work in polymeric chemistry and chemical engineering helped pave the way for his team’s notable discovery. Polymers are fairly large molecules linked like beads on a necklace that exist in nearly everything, from DNA to silk and plastics like polypropylene. Their molecular chain-line dynamics possess a “magic,” Rosenboom says.
“Polymers are fascinating because you can make almost any type of material with them—hard or soft, durable or degradable, porous or impermeable, hydrophobic or hydrophilic, and so on,” says Rosenboom, who was a 2023 MIT Koch Institute Ludwig Center Scholar. “And all of that is largely guided by two things: their chemical composition and their length. Tuning these aspects carefully, you can make highly useful materials for people and the planet—delivering drugs in a more effective way and creating fully circular plastic without carbon emissions.”
Modifying gel properties
One of the main hurdles in designing a gel-based drug delivery system was that it needed to transform from an injectable liquid at room temperature outside the body to a heavily viscous form at body temperature inside the body—one that could hold a drug and an imaging agent. That near-solid form would prevent leakage, allowing for the drug’s controlled release and visible confirmation of its delivery to the targeted tumor.
The delivery system would have to be safe and degrade over time, so it wouldn’t stay in the body forever, like synthetic plastics lingering in the environment. For Rosenboom, who has researched bioplastics recycling and sustainability, this was a new and fascinating challenge.
His research team included medical doctors and chemical engineers and took about four years to develop the new form of hydrogel. Using a finely tuned formulation of biodegradable polymers sensitive to heat, they were able to load the gel with a high concentration but small volume of an immunotherapy drug and a contrast agent.
They discovered that slightly changing the polymer’s chain length makes it possible for the hydrogel to shift from liquid to nearly solid once it warms from room to body temperature. It forms a heavily viscous nanoparticle around the water-repellent immunotherapy drug, which keeps the medication in place to be slowly released over several days and observed by clinicians. After helping to harness the body’s immune system to fight cancer, the gel safely dissipates.
Making new bonds
Rosenboom’s expertise in polymers extends to the use of chemistry to develop fully circular and sustainable bioplastics. As a PhD student at ETH Zurich in Switzerland, he developed a new way to make polyethylene furanoate (PEF), a bio-based polymer alternative to polyethylene terephthalate (PET) plastic. Working with a Swiss engineering firm to scale up, his team produced high-quality, virgin-grade recycled PET from plastic and polyester waste using a simpler process and lower carbon emissions than traditional plastic recycling, which is less effective at preventing waste.
The technology forms the basis for Rosenbloom’s recently founded startup, MacroCycle Technologies, at MIT’s The Engine Accelerator. Less energy-intensive and carbon-emitting than chemical-based recycling technologies, the process uses a patented nontoxic solvent to dissolve and reassemble plastics in a liquid state in less than 10 hours, about half the time it typically takes to fuse entirely new chains of polymers using a solid-state, mechanical recycling method of shredding, melting, and then tumbling pellets.
“We’re doing things a little differently,” says Rosenboom, who has given two TEDx talks about carbon-negative plastic recycling technology and served as a plastic recycling consultant to Apple for two years. “We’re not breaking bonds, we’re making new ones.”
Impact with passion
Between drug delivery and circular upcycling, Rosenboom appears to be following advice he once received from Professor Langer: “Focus on the big problems.”
“Bob’s words often ring in my head and help me with three things: discipline, motivation, and perspective,” he says. “Discipline to choose the most important tasks at hand on a daily basis, since we only have so much time in a day, and there are a lot of distractions, and motivation to work a lot fueled with passion, since I feel that my efforts can one day resolve big global challenges.”