Lay summary
Cancer is a leading cause of death in New Zealand and worldwide. Immunotherapy, although revolutionary in many cancer types, benefits only 10-40% of cancer patients. The clinical response of immunotherapy primarily depends on cytotoxic lymphocyte infiltration to recognise and kill cancer cells. However, in solid tumours, abnormal vasculature and dense stroma constitute a formidable physical barrier that strikingly limits lymphocyte infiltration, undermining therapeutic efficacy. To enhance lymphocyte infiltration for cancer immunotherapy, our research aims to synthesise a series of conjugates by linking nitric oxide donors with certain immunomodulatory drugs and then develop a bioinspired therapeutic nanosystem that facilitates their deep penetration and preferential accumulation within tumours. The release of these active agents will lead to remodelling of the intricate physical tumour barrier, thereby improving lymphocyte infiltration and synergistically increasing the efficacy of solid tumour immunotherapy agents.