Liu Yunpeng, Zhang Ting, Jiao Yan, Li Hongru, Xie Cheng, Liu Yahui, Cai Hongqiao
Department of Thoracic Surgery, The First Hospital of Jilin University, 1 Xinmin Street, Changchun 130021, China.
Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, the First Hospital of Jilin University, 1 Xinmin Street, Changchun 130021, China.
Colloids Surf B Biointerfaces. 2025 Dec;256(Pt 2):115003. doi: 10.1016/j.colsurfb.2025.115003. Epub 2025 Aug 5.
Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases, in urgent need for multimodal therapeutic strategies. Sonodynamic therapy (SDT) has recently emerged as a promising non-invasive strategy. Programmed death-ligand 1 (PD-L1) antibody represented immunotherapy has shown limited efficacy due to inadequate tumor accumulation and persistent intracellular PD-L1 signaling. To address these challenges, we developed a multifunctional biomimetic nanodrug (APSNM), composed of iron phthalocyanine (FePc)-silicate nanoparticle (NP) and encapsulated Anlotinib, with PD-L1 coated macrophage membrane onto the surface. This design enables dual checkpoint inhibition by concurrently downregulating intracellular PD-L1 via p-VEGFR2/p-JAK2/p-STAT3 pathway suppression and blocking extracellular PD-L1 through antibody-mediated surface binding. Upon ultrasound activation, APSNM generates reactive oxygen species (ROS) and enhances antitumor immunity. Orthotopic lung tumor mouse model demonstrates that APSNM exhibits excellent tumor-targeting capability and enhanced antitumor efficacy compared to non-functionalized or non-ultrasound-treated controls. Notably, APSNM + US treatment led to the greatest tumor regression, increased CD4 and CD8 T cell infiltration, and elevated IFN-γ expression. These findings highlight APSNM as a promising nanoplatform for precise, multimodal NSCLC therapy via the integration of antiangiogenesis, sonodynamic therapy, and immune checkpoint modulation.
非小细胞肺癌(NSCLC)约占所有肺癌病例的85%,迫切需要多模式治疗策略。声动力疗法(SDT)最近已成为一种有前景的非侵入性策略。以程序性死亡配体1(PD-L1)抗体为代表的免疫疗法由于肿瘤蓄积不足和细胞内PD-L1信号持续存在,疗效有限。为应对这些挑战,我们开发了一种多功能仿生纳米药物(APSNM),它由铁酞菁(FePc)-硅酸盐纳米颗粒(NP)组成,并包裹了安罗替尼,表面涂有PD-L1包被的巨噬细胞膜。这种设计通过抑制p-VEGFR2/p-JAK2/p-STAT3途径同时下调细胞内PD-L1以及通过抗体介导的表面结合阻断细胞外PD-L1,实现双重检查点抑制。在超声激活后,APSNM产生活性氧(ROS)并增强抗肿瘤免疫力。原位肺肿瘤小鼠模型表明,与未功能化或未超声处理的对照相比,APSNM具有出色的肿瘤靶向能力和增强的抗肿瘤疗效。值得注意的是,APSNM + US治疗导致最大程度的肿瘤消退、CD4和CD8 T细胞浸润增加以及IFN-γ表达升高。这些发现突出了APSNM作为一种有前景的纳米平台,可通过整合抗血管生成、声动力疗法和免疫检查点调节来实现精确的多模式NSCLC治疗。