Cutting-edge microparticles can deliver two cancer treatments at once

Patients with advanced cancer often face a difficult journey with limited treatment options. Standard therapies—like chemotherapy, surgery, and radiation—can result in severe side effects without guaranteeing the desired outcome.

For some patients, traditional treatments alone may not be enough to halt the rapid growth of aggressive tumors, leaving them with few alternatives. To address this challenge, researchers at MIT have designed an innovative treatment approach that may open new doors for late-stage cancer patients.

This approach combines heat-based therapy, or phototherapy, and chemotherapy, offering a dual-action method for more targeted, effective cancer treatment.

Led by MIT’s Koch Institute for Integrative Cancer Research, the team developed microparticles designed to be implanted at the tumor site. Here, the particles release two types of therapy: localized heat and chemotherapy drugs.

This combination therapy aims to reduce side effects typically associated with intravenous chemotherapy and potentially improve survival outcomes by delivering treatment directly to the tumor. In early tests, this innovative therapy completely eliminated tumors in mice and significantly prolonged their lifespan.

Ana Jaklenec, a principal investigator at MIT, sees particular promise in treating fast-growing, high-risk tumors. “The goal would be to gain some control over these tumors for patients that don't really have a lot of options,” Jaklenec explains. “This could either prolong their life or at least allow them to have a better quality of life during this period.”

Jaklenec co-authored the study alongside Angela Belcher, MIT’s James Mason Crafts Professor of Biological Engineering and Materials Science, and MIT Institute Professor Robert Langer. Former MIT postdoc Maria Kanelli is the lead author of this groundbreaking study, recently published in ACS Nano.

Phototherapy, a relatively new treatment method, involves implanting or injecting particles that can be heated with a laser, raising their temperature enough to kill nearby tumor cells without harming surrounding tissue. Current phototherapy approaches in clinical trials use gold nanoparticles, which emit heat when exposed to near-infrared light.

The MIT research team, however, sought to combine phototherapy with chemotherapy to enhance the treatment's effectiveness. They selected an inorganic material called molybdenum sulfide as the phototherapeutic agent. Unlike gold, molybdenum sulfide is highly efficient at converting laser light to heat, allowing for the use of low-powered lasers in the process.

To develop particles that could deliver both heat and chemotherapy, researchers created microparticles that incorporated molybdenum disulfide nanosheets along with a chemotherapy drug. Two drugs were tested: doxorubicin, which is water-soluble, and violacein, which is water-insoluble.

The researchers mixed molybdenum disulfide and the selected chemotherapy drug with a polymer, polycaprolactone, and dried it into a film, which could then be shaped into particles.

The team chose 200-micrometer-wide cubic particles, which, once injected at the tumor site, remain there throughout the treatment. During each session, an external near-infrared laser heats the particles. This laser can penetrate a few millimeters to centimeters into the tissue, focusing on the local tumor area.

Maria Kanelli, the lead author, explains the unique advantage of this approach: “You administer it once through an intratumoral injection, and then using an external laser source you can activate the platform, release the drug, and at the same time achieve thermal ablation of the tumor cells.” This dual effect targets the tumor on demand, providing a pulsatile release of therapy and reducing the overall strain on the patient.

Determining the ideal laser power, exposure time, and concentration of the phototherapeutic agent is crucial to the success of the dual therapy. The team used machine-learning algorithms to optimize these parameters for the best treatment outcome.

Their findings led to a three-minute treatment protocol, where the laser heats the particles to around 50 degrees Celsius. This temperature is high enough to kill tumor cells while simultaneously melting the polymer, releasing the embedded chemotherapy drug into the tumor.

Neelkanth Bardhan, a research scientist in Belcher's lab, highlights the benefits of this system: “This machine-learning-optimized laser system really allows us to deploy low-dose, localized chemotherapy by leveraging the deep tissue penetration of near-infrared light for pulsatile, on-demand photothermal therapy. This synergistic effect results in low systemic toxicity compared to conventional chemotherapy regimens.”

The researchers tested their microparticles in mice with triple-negative breast cancer—a particularly aggressive cancer type with limited treatment options. After tumors developed, the team implanted around 25 microparticles into each tumor. They then treated each tumor with a laser three times, spaced three days apart.

Angela Belcher, a senior author of the study, describes the promising results: “This is a powerful demonstration of the usefulness of near-infrared-responsive material systems. Controlling the drug release at timed intervals with light, after just one dose of particle injection, is a game changer for less painful treatment options and can lead to better patient compliance.”

In mice receiving the dual therapy, tumors were completely eliminated, and these mice lived significantly longer than those receiving chemotherapy or phototherapy alone. Mice treated with three full cycles also fared better than those given just one laser treatment. The success of the microparticles in eradicating tumors and prolonging survival in animal models holds promise for future treatments in human patients.

The polymer used in these microparticles, polycaprolactone, is biocompatible and has already been FDA-approved for other medical applications, such as in implantable medical devices. With promising results in hand, the MIT team is preparing to test this dual-therapy approach in larger animal models. Ultimately, they aim to initiate clinical trials, potentially bringing this therapy to human patients.

Researchers believe that this dual-treatment platform could be used for many types of solid tumors, including metastatic tumors that spread from their original site. The approach could serve as a lifeline for patients with limited options, offering an alternative treatment that is both effective and less taxing on the body.

The study, which received funding from organizations including the Bodossaki Foundation, the Onassis Foundation, the Mazumdar-Shaw International Oncology Fellowship, and the National Cancer Institute, marks a significant step forward in the fight against cancer.

With further testing, this innovative technology may become an essential part of the future cancer treatment landscape, helping to improve both the quality and length of life for patients worldwide.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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