SBIR Phase I: The TPMAL Platform for Targeted Delivery of Photodynamic Therapy and Chemotherapy to Peritoneal Metastasis

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project focuses on advancing a novel light-activatable nanoplatform to improve the management of peritoneal metastasis and enhance patient quality of life. Peritoneal metastasis is a common pattern of disease spread in advanced gynecological and gastrointestinal cancers. There are nearly 1.2 million patients globally, with around 75,000 new cases diagnosed annually in the United States. Specifically, colorectal peritoneal metastasis remains particularly challenging to treat, with a high recurrence rate of over 65%. Unfortunately, the overall survival and disease management has only modestly improved in the past 30 years. The U.S. peritoneal cancer market is projected to reach approximately USD 1.0 billion by 2030, with a compound annual growth rate of 9.1% from 2024 to 2030. This underscores the urgent therapeutic and economic need for innovative strategies to treat colorectal peritoneal metastasis. One promising clinical advancement is intraperitoneal photodynamic therapy (PDT), which can be integrated into standard laparotomy or laparoscopic procedures. Currently, there are over 100 active or recruiting clinical trials related to PDT. This nanoplatform enables efficient co-delivery of PDT and chemotherapy to selectively target cancer cells that could not be removed by surgery, potentially improving patient survival. This Small Business Innovation Research (SBIR) Phase I project will help bridge the translational gap of a novel light-activatable nanoplatform, facilitating its successful commercialization for the treatment of peritoneal metastasis. The nanoplatform is designed for the targeted co-delivery of PDT and chemotherapy to eliminate tumors left after surgery. The nanoplatform combines antibody-photosensitizer conjugates and liposomal chemotherapy to enhance the safety and efficacy of PDT. Following injection, harmless red-light selectivity activates PDT within cancer cells, inducing cancer cell death while minimizing damage to healthy cells. This Phase I project will help de-risk the translation of the nanoplatform from bench to bedside by developing a scale able manufacturing process, determining the optimal drug administration route, and identifying PDT threshold. To achieve these goals, the key objectives are to: 1) Compare the pharmacokinetics and biodistribution of the nanoplatform following intravenous or intraperitoneal administration, and 2) Establish the photobleaching threshold of PDT. Insights from this study will accelerate clinical translation and ultimately provide surgeons with an alternative treatment for peritoneal metastasis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.