The limited lymphocytes infiltration and immunosuppression in tumor are the major challenges of cancer immunotherapy. The use of immunogenic cell death (ICD)‐inducing agents has potential to potentiate antitumor immune responses, but is tremendously hampered by the poor delivery efficiency. Herein, a tumor‐activated size‐enlargeable bioinspired lipoprotein of oxaliplatin (TA‐OBL) is designed to access cancer cells and boost the ICD‐induced antitumor immunity for synergizing immune‐checkpoint blockades (ICBs)‐mediated immunotherapy. TA‐OBL is constructed by integrating a legumain‐sensitive melittin conjugate for improving intratumoral permeation and cancer cell accessibility, a pH‐sensitive phospholipid for triggering size‐enlargement and drug release in intracellular acidic environments, a nitroreductase‐sensitive hydrophobic oxaliplatin prodrug (N‐OXP) for eliciting antitumor immunity into the bioinspired nano‐sized lipoprotein system. TA‐OBL treatment produced robust antitumor immune responses and its combination with ICBs demonstrates strong therapeutic benefits with delayed tumor growth and extended survival rate, making it a promising delivery nanoplatform to elicit antitumor immunity for cancer immunotherapy.

中文翻译：

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肿瘤激活的大小可放大的仿生脂蛋白进入肿瘤中的癌细胞以引发抗肿瘤免疫反应

肿瘤中有限的淋巴细胞浸润和免疫抑制是癌症免疫治疗的主要挑战。使用免疫原性细胞死亡 (ICD) 诱导剂具有增强抗肿瘤免疫反应的潜力，但由于递送效率低下而受到极大阻碍。在此，奥沙利铂（TA-OBL）的肿瘤激活大小可放大的生物启发脂蛋白旨在进入癌细胞并增强ICD诱导的抗肿瘤免疫，以协同免疫检查点阻断（ICBs）介导的免疫治疗。TA-OBL 是通过整合 Legumain 敏感的蜂毒肽偶联物来构建的，用于改善肿瘤内渗透和癌细胞可及性，一种 pH 敏感的磷脂，用于在细胞内酸性环境中触发尺寸增大和药物释放，一种硝基还原酶敏感的疏水性奥沙利铂前药（N-OXP），用于在受生物启发的纳米级脂蛋白系统中引发抗肿瘤免疫。TA-OBL 治疗产生了强大的抗肿瘤免疫反应，其与 ICBs 的组合显示出强大的治疗益处，具有延迟肿瘤生长和延长存活率，使其成为一种有前景的递送纳米平台，用于引发癌症免疫治疗的抗肿瘤免疫。