Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan–dextran-based magnetic nanomedicine (IO@FuDex³) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex³ can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects. Treatment that combines IO@FuDex³ and magnetic navigation reduces the occurrence of adverse events and extends the median survival from 32 to 63 days with less than 1 per cent dose compared with soluble anti-PD-L1. Thus, we demonstrate the potential of integrating anti-PD-L1 and T-cell activators as a form of inherently therapeutic nanomedicine to augment the therapeutic index of combination checkpoint immunotherapy.

抑制肿瘤免疫逃避的检查点免疫疗法已经证明了显着的临床成功。然而，治疗反应仅限于某些患者群体，免疫毒性和自身免疫损害了治疗效果。在这里，我们报告了一种与检查点抑制剂（抗 PD-L1）和 T 细胞激活剂（抗 CD3 和抗 CD28）结合的固有治疗性基于岩藻多糖-葡聚糖的磁性纳米药物（IO@FuDex ³）。IO@FuDex ³可以通过重振肿瘤浸润淋巴细胞来修复免疫抑制性肿瘤微环境，同时通过磁导航将纳米药物靶向肿瘤以最大限度地减少脱靶效应。结合 IO@FuDex ^{3 的}治疗与可溶性抗 PD-L1 相比，磁导航减少了不良事件的发生，并将中位生存期从 32 天延长至 63 天，剂量不到 1%。因此，我们证明了将抗 PD-L1 和 T 细胞激活剂整合为一种固有治疗性纳米药物的潜力，以增加联合检查点免疫疗法的治疗指数。