锰基免疫放大器纳米平台用于腹膜转移性结直肠癌化学免疫治疗

Abstract

Current immunotherapies exhibit limited clinical efficacy in patients with colorectal cancer (CRC). While manganese ions (Mn) can activate the cGAS–STING pathway to potentiate innate immunity, their clinical application is limited by poor tumor accumulation and potential systemic toxicity. Alendronate (ALN), an FDA-approved agent, exerts T cell immunomodulatory activity but is hampered by low bioavailability and undesired bone targeting. To effectively potentiate antitumor immunity against CRC, we developed a manganese-alendronate (MnALN) nanomedicine via infinite coordination, leveraging Mn and ALN to synergistically eliminate tumor cells. In addition, Mn triggers reactive oxygen species (ROS)–mediated endoplasmic reticulum (ER) stress and subsequent immunogenic cell death (ICD) in tumor cells, while its combination with ALN further enhances T cell immune responses, ultimately achieving efficient tumor growth inhibition and intense anti-tumor immune response. This study presented a dual-functional MnALN nanomedicine synthesized from clinically available Mn and ALN, simultaneously activating apoptosis and inflammation-related pathways in CRC cells, which provides an effective strategy for immune tolerance CRC therapy.