Abstract：
Therapy-induced immunogenic cell death (ICD) can initiate both innate and adaptive immune responses for amplified anti-tumor efficacy. However, dying cell-released ICD signals are prone to being sequestered by the TIM-3 receptors on dendritic cell (DC) surfaces, preventing immune surveillance. Herein, dismantlable coronated nanoparticles (NPs) are fabricated as a type of spatiotemporally controlled nanocarriers for coupling tumor cell-mediated ICD induction to DC-mediated immune sensing. These NPs are loaded with an ICD inducer, mitoxantrone (MTO), and wrapped by a redox-labile anti-TIM-3 (αTIM-3) antibody corona, forming a separable core-shell structure. The antibody corona disintegrates under high levels of extracellular reactive oxygen species in the tumor microenvironment, exposing the MTO-loaded NP core for ICD induction and releasing functional αTIM-3 molecules for DC sensitization. Systemic administration of the coronated NPs augments DC maturation, promotes cytotoxic T cell recruitment, enhances tumor susceptibility to immune checkpoint blockade, and prevents the side effects of MTO. This study develops a promising nanoplatform to unleash the potential of host immunity in cancer therapy.
摘要：
治疗诱导的免疫原性细胞死亡（ICD）可以引发先天和适应性免疫反应，以增强抗肿瘤功效。然而,垂死细胞释放的ICD信号容易被树突状细胞（DC）表面的TIM-3受体隔离，防止免疫监视。在这里，可拆除的冠状纳米粒子（NPs）是一种时空控制的纳米载体，用于将肿瘤细胞介导的ICD诱导与DC介导的免疫传感耦合。这些NP装有ICD诱导器，米托蒽醌(MTO),并由氧化还原不稳定的抗TIM-3（αTIM-3）抗体电晕包裹，形成可分离的核-壳结构。抗体电晕在肿瘤微环境中高水平的细胞外活性氧下崩解，暴露MTO负载的NP核心用于ICD诱导，并释放功能性αTIM-3分子用于DC敏化。全身施用加冕的NP会增加DC的成熟，促进细胞毒性T细胞募集，增强肿瘤对免疫检查点阻断的易感性，并防止MTO的副作用。这项研究开发了一个有前途的纳米平台，以释放宿主免疫在癌症治疗中的潜力。本文受版权保护。保留所有权利。
