MIT researchers have engineered implantable microparticles capable of delivering dual cancer therapy—combining heat and chemotherapy—directly to tumor sites. This innovative approach aims to improve treatment outcomes while reducing systemic side effects. In a study on mice with aggressive triple-negative breast tumors, the dual therapy led to complete tumor eradication and significantly prolonged survival, marking a potential breakthrough in cancer treatment.
Dual-Action Microparticles for Targeted Therapy
The microparticles are designed to release chemotherapy drugs and generate heat upon exposure to an external near-infrared laser. Molybdenum disulfide nanosheets serve as the phototherapeutic agent, efficiently converting laser light into heat. The particles are combined with either doxorubicin (hydrophilic) or violacein (hydrophobic) and encapsulated in a polycaprolactone polymer matrix. Once injected into a tumor, these cubic particles (200 micrometers wide) remain in place, allowing for repeated treatment cycles.
Maria Kanelli, the lead author of the ACS Nano paper, explains, "The advantage of this platform is that it can act on demand in a pulsatile manner. 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."
Optimized Treatment Protocol
To maximize treatment efficacy, the researchers employed machine-learning algorithms to optimize laser power, irradiation time, and the concentration of the phototherapeutic agent. The optimized laser treatment cycle lasts approximately three minutes, during which the particles are heated to 50 degrees Celsius. This temperature is sufficient to kill tumor cells and trigger the release of chemotherapy drugs from the polymer matrix.
Neelkanth Bardhan, a research scientist in the Belcher Lab, notes, "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."
Preclinical Efficacy
The microparticle treatment was tested in mice injected with aggressive triple-negative breast cancer cells. After tumors developed, approximately 25 microparticles were implanted per tumor, followed by three laser treatments spaced three days apart. The results were striking: tumors were completely eradicated in the treated mice, and their survival was significantly longer compared to mice receiving chemotherapy or phototherapy alone, or no treatment at all.
Angela Belcher, the James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering, emphasizes the potential of this approach: "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."
Future Directions
Given the biocompatibility of the polycaprolactone polymer (already FDA-approved for medical devices), the researchers are optimistic about translating this technology to clinical trials. They plan to conduct further testing in larger animal models, with the ultimate goal of evaluating the microparticles in human patients. The treatment is expected to be applicable to various solid tumors, including metastatic lesions, offering a new avenue for cancer therapy.
