Wang Linbang, Liu Yu, Wang Ziyu, Liu Jingkun, Yan Ziqiang, Liu Xiaoguang
Department of Orthopedics, Peking University Third Hospital, Beijing, People's Republic of China.
Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, No. 555, Youyi Road, Beilin District, Xi'an, 710054 Shaanxi People's Republic of China.
Mater Today Bio. 2025 Aug 30;34:102231. doi: 10.1016/j.mtbio.2025.102231. eCollection 2025 Oct.
Although immunotherapy exhibits remarkable clinical potential for the treatment of tumors, immune responses generated by conventional approaches often fail to completely eradicate osteosarcoma. This inadequacy stems primarily from the low immunogenicity of osteosarcoma-derived neoantigens and the limitations of conventional strategies that focus on enhancing only a single step in the tumor immunity cycle and fail to effectively drive a comprehensive immune response. To address these challenges and augment antitumor immune responses, we developed the innovative core-shell nanoparticle system BaTiO3-indisulam@PD1-cell Membrane Nanoparticles (BI@PCM NPs). This system achieves tumor targeting and enables the ultrasound-triggered controlled release of components. Unlike traditional methods that rely on DNA damage-mediated neoantigen production, BI@PCM disrupts alternative RNA splicing, thereby generating high-quality Endogenous Tumor Neoantigens (ETNs). These ETNs are dynamically transported from the tumor site to lymph nodes (LNs) using BaTiO nanocubes (≈10 nm) as efficient nanocarriers. BaTiO acts as a piezoelectric catalyst, producing reactive oxygen species (ROS) upon ultrasound stimulation, further enhancing the immunogenic death of osteosarcoma cells. Integration of Pd1 cell membrane coating provides enhanced targeting capabilities and significantly amplifies cytotoxic T-cell activation. By strengthening multiple immune cycle steps, BI@PCM exhibits immense potential to revolutionize personalized tumor immunotherapy and provide a robust solution for osteosarcoma treatment.
尽管免疫疗法在肿瘤治疗中展现出显著的临床潜力，但传统方法所引发的免疫反应往往无法完全根除骨肉瘤。这种不足主要源于骨肉瘤衍生新抗原的低免疫原性，以及传统策略的局限性，这些策略仅专注于增强肿瘤免疫循环中的单个步骤，而未能有效驱动全面的免疫反应。为应对这些挑战并增强抗肿瘤免疫反应，我们开发了创新的核壳纳米颗粒系统——钛酸钡-茚地那韦@PD1-细胞膜纳米颗粒（BI@PCM NPs）。该系统实现了肿瘤靶向，并能实现超声触发的成分控释。与依赖DNA损伤介导新抗原产生的传统方法不同，BI@PCM破坏了可变RNA剪接，从而产生高质量的内源性肿瘤新抗原（ETNs）。这些ETNs以约10纳米的钛酸钡纳米立方体作为高效纳米载体，从肿瘤部位动态转运至淋巴结（LNs）。钛酸钡作为压电催化剂，在超声刺激下产生活性氧（ROS），进一步增强骨肉瘤细胞的免疫原性死亡。整合的Pd1细胞膜涂层提供了增强的靶向能力，并显著放大细胞毒性T细胞的激活。通过强化多个免疫循环步骤，BI@PCM在革新个性化肿瘤免疫疗法以及为骨肉瘤治疗提供强大解决方案方面展现出巨大潜力。
