该研究设计了一种 基于多肽 接枝聚合物 的纳米机器人 （ peptide-grafted polymer-based nanorobot ） ，它能够在阻断 PD-1/PD-L1 的同时； 通过一个 pH 响应模块原位形成纤维来 破坏癌细胞膜 ，诱导 免疫原性细胞死亡 （ICD） ，释放 损伤相关分子模式 （DAMP） ，招募 T 细胞浸润。从而双管齐下 （解除 刹车+踩下油门） 发挥抗癌作用。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 目前，阻断 PD-1 及其受体 PD-L1 为癌症治疗带来了巨大前景。尽管 PD-1/PD-L1 阻断疗法在临床上对多种类型的癌症的治疗取得了令人振奋的进展，但超过 95% 的 结直肠癌 （CRC） 患者属于错配修复功能正常 （pMMR） 的" 冷肿瘤 "，其对 PD-1/PD-L1 阻断疗法无响应，因为免疫细胞几乎无法浸润到免疫抑制 性的肿瘤微环境 （TME） 中。 诸如化疗、放疗和光热疗法之类的策略有可能通过免疫原性细胞死亡 （ICD） 和损伤相关分子模式 （DAMP） 的释放，将 pMMR 型"冷肿瘤"逆转为"热肿瘤"， 从而重塑肿瘤微环境，使癌细胞对基于 PD-1/PD ...

Core Viewpoint - The article discusses a novel approach to enhance CD47 blockade therapy for cancer treatment by utilizing biomineralized nanoparticles that facilitate phagocytosis and mitochondrial DNA sensing, leading to improved therapeutic outcomes [2][5]. Group 1: Research Background - Antigen-presenting cells (APCs) mediate the phagocytosis of cancer cells and initiate antigen presentation through sensing mitochondrial DNA (mtDNA), which is a critical mechanism in CD47 blockade therapy [2]. - Current strategies targeting CD47 often lack regulation of mtDNA sensing, limiting their effectiveness [2]. Group 2: Research Findings - The study developed biomineralized nanoparticles ZnCO₃@BSA/siCD47 that enhance CD47 blockade therapy by promoting APC phagocytosis and mtDNA sensing, resulting in significant tumor growth inhibition [2][5]. - The nanoparticles are designed to balance the stable encapsulation of siRNA with efficient intracellular release, achieving effective CD47 silencing and Zn²⁺ overload [5][6]. - In colorectal cancer and melanoma models, ZnCO₃@BSA/siCD47 restored APC function, increased T cell infiltration, and achieved a tumor growth inhibition rate of 93% [5][6]. Group 3: Mechanism of Action - The strategy involves Zn²⁺ overload to enhance phagocytosis and STING activation, while the pH-responsive ZnCO₃@BSA matrix ensures synchronized delivery of Zn²⁺ and siRNA [6]. - The treatment induces CD47 knockdown, calreticulin exposure, and mtDNA release, which are crucial for effective immune response [6].