AN INJECTABLE HYDROGEL FOR OXYGEN DELIVERY AND PHOTOTHERMAL THERAPY IN PANCREATIC CANCER

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with a dismal 5-year survival rate of approximately 10%, largely due to its exceptionally hostile tumor microenvironment. Rapid proliferation, severe hypoxia and dense desmoplasia not only impede the efficacy of conventional therapies but also drive T cell exhaustion, further limiting antitumor immunity and highlighting the urgent need for integrated, microenvironment-targeted interventions. This project aims to develop an injectable hydrogel platform for localized modulation of the PDAC microenvironment through controlled oxygen generation, photothermal therapy, and manganese-mediated immunomodulation. The in situ–forming hydrogel will enable minimally invasive intratumoral or peritumoral administration, bypassing the limitations of systemic delivery. It will incorporate graphene oxide as a near-infrared photothermal agent capable of inducing tumor ablation, as well as disrupting the stromal network, and biodegradable PLGA microparticles co-encapsulating calcium peroxide and manganese dioxide. Calcium peroxide reacts with water to generate hydrogen peroxide, which is subsequently decomposed by manganese dioxide to yield oxygen, while simultaneously releasing Mn²⁺ ions that activate innate antitumor immunity via the cGAS-STING pathway. By combining localized oxygenation, photothermally induced tumor ablation, and controlled Mn²⁺ release in a single injectable construct, this platform addresses both the physical and immunological barriers characteristic of PDAC, with potential for future integration with immunotherapies or molecularly targeted oncology approaches, offering a versatile and novel platform against PDAC.