In situ thermal-responsive hydrogels for combined photothermal therapy and chemotherapy of pancreatic cancer

Abstract

Pancreatic cancer is a malignancy with a poor prognosis and high mortality. Survival outcomes remain very poor despite significant advances in molecular diagnostics and therapeutics in clinical practice. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage, and most cancers recur after surgery. Treatments other than surgery, including chemotherapy and immunotherapy, still offer disappointing results. Multidisciplinary treatment approaches through appropriate carriers have provided new solutions for improving the prognosis of pancreatic cancer. Herein, we reported an in situ formed thermo-responsive hybrid hydrogel loaded with gemcitabine and manganese dioxide nanoparticles, which exhibited good injectability, high photothermal hyperthermia, and biocompatibility, leading to efficient multidisciplinary treatment of pancreatic cancer in combination with chemotherapy and photothermal therapy (PTT). The hybrid hydrogel could be heated to 51 °C under 808 nm laser irradiation in five minutes. In situ intratumoral injection results suggested that the hybrid hydrogel exhibited high photothermal efficiency in killing rabbit pancreatic tumors. In vivo results indicated that the multidisciplinary treatment almost completely eliminated subcutaneous tumors in mice within 14 days. This development offers an efficient multidisciplinary treatment for pancreatic cancer.