MIT researchers have engineered implantable microparticles capable of delivering both chemotherapy and photothermal therapy directly to tumor sites. This innovative approach aims to enhance treatment efficacy while minimizing systemic side effects commonly associated with traditional cancer therapies.
The microparticles, described in a recent ACS Nano paper, combine molybdenum disulfide nanosheets with chemotherapeutic drugs such as doxorubicin or violacein. Molybdenum disulfide efficiently converts laser light into heat, enabling photothermal ablation of tumor cells. The particles are designed to release the chemotherapeutic agent upon laser activation, creating a synergistic therapeutic effect.
Microparticle Design and Mechanism
The microparticles are fabricated by mixing molybdenum disulfide and the chemotherapeutic drug with polycaprolactone, a biocompatible polymer. This mixture is then dried into a film and processed into cubic microparticles approximately 200 micrometers in width. Once injected into the tumor, these particles remain localized, allowing for targeted treatment.
During treatment, an external near-infrared laser heats the particles to around 50 degrees Celsius. This temperature is sufficient to kill tumor cells and trigger the release of the encapsulated chemotherapy drug. The laser's penetration depth, ranging from millimeters to centimeters, ensures localized impact on the tumor tissue.
Maria Kanelli, the lead author of the study, highlights the on-demand, pulsatile nature of the platform, "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."
Preclinical Efficacy
The researchers evaluated the microparticle treatment in mice bearing aggressive triple-negative breast tumors. Following tumor formation, approximately 25 microparticles were implanted per tumor, and laser treatment was administered three times, with three-day intervals between sessions. The treatment protocol was optimized using machine-learning algorithms to determine the ideal laser power, irradiation time, and concentration of the phototherapeutic agent.
The results demonstrated complete tumor eradication in the majority of treated mice. Moreover, these mice exhibited significantly prolonged survival compared to those receiving chemotherapy or photothermal therapy alone, or no treatment at all. Mice undergoing all three laser treatment cycles showed superior outcomes compared to those receiving only one cycle.
Clinical Potential
The biocompatibility of polycaprolactone, already FDA-approved for medical devices, supports the translational potential of this technology. The researchers plan to conduct further testing in larger animal models, with the ultimate goal of clinical trials. They anticipate that this treatment approach could be applicable to various solid tumors, including metastatic lesions.
Angela Belcher, a senior author of the study, emphasizes the significance of light-controlled drug release, "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."
