Zhang Zhenghua, Tian Yang, Gao Wenjun, Hu Yubin, Luo Liangping, Lei Lichang, Shen Shasha, Han Dan
Medical Imaging Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Radiology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Front Chem. 2024 Dec 2;12:1508912. doi: 10.3389/fchem.2024.1508912. eCollection 2024.
Immune checkpoint inhibitors (ICIs) have demonstrated potential in inhibiting the growth of malignant pleural mesothelioma (MPM), and their efficacy is associated with the expression of programmed death-ligand 1(PD-L1). This study evaluated a PD-L1-targeted nanoprobe for detecting PD-L1 expression in a nude mouse model of malignant pleural mesothelioma (MPM).
A PD-L1-binding peptide (WL-12) was conjugated with superparamagnetic iron oxide nanoparticles (SPIONs) to create the nanoprobe WL-12@Fe₃O₄. The nanoprobe's stability, biotoxicity, targeting ability, and magnetic resonance (MR) imaging effects were assessed and compared to non-targeted Fe₃O₄ nanoparticles. ΔT2 values and PD-L1 expression were measured in H226 and MSTO-211H tumor tissues over 4 weeks to analyze correlations.
The WL-12@Fe₃O₄ nanoprobe demonstrated uniform distribution and a spherical shape, with a larger size (43.82 nm) and lower surface potential (-9.34 ± 0.54 mV) compared to Fe₃O₄ (32.67 nm, -20.20 ± 0.88 mV, < 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with FeO It was well dispersed in serum and saline and showed no cytotoxicity or organ damage . The probe selectively accumulated in PD-L1-expressing MPM cells, especially MSTO-211H, and exhibited significantly higher uptake in high PD-L1-expressing H460 cells (930.22 ± 11.75 ng/mL) compared to low PD-L1-expressing A549 cells (254.89 ± 17.33 ng/mL, < 0.05). Tumor iron levels in the WL-12@Fe₃O₄ group were significantly elevated (141.02 ± 17.33 μg/g) compared to controls (36.43 ± 3.56 μg/g, < 0.05), with no significant differences in other organs ( > 0.05). The T2 values of H226 and MSTO-211H tumors decreased after probe injection, with ΔT2 values significantly higher in the targeted group than the nontargeted group ( < 0.05). ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression ( < 0.05).
The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.
免疫检查点抑制剂已显示出抑制恶性胸膜间皮瘤（MPM）生长的潜力，其疗效与程序性死亡配体1（PD-L1）的表达有关。本研究评估了一种靶向PD-L1的纳米探针，用于在恶性胸膜间皮瘤（MPM）裸鼠模型中检测PD-L1表达。
将一种PD-L1结合肽（WL-12）与超顺磁性氧化铁纳米颗粒（SPIONs）偶联，制备纳米探针WL-12@Fe₃O₄。评估该纳米探针的稳定性、生物毒性、靶向能力和磁共振（MR）成像效果，并与非靶向Fe₃O₄纳米颗粒进行比较。在4周内测量H226和MSTO-211H肿瘤组织中的ΔT2值和PD-L1表达，以分析相关性。
WL-12@Fe₃O₄纳米探针呈均匀分布且为球形，与Fe₃O₄相比尺寸更大（43.82 nm），表面电位更低（-9.34±0.54 mV）（Fe₃O₄为32.67 nm，-20.20±0.88 mV，P<0.05）。XPS和FT-IR分析结果表明WL-12与Fe₃O₄成功偶联。它在血清和盐水中分散良好，未显示出细胞毒性或器官损伤。该探针选择性地积聚在表达PD-L1的MPM细胞中，尤其是MSTO-211H，与低表达PD-L1的A549细胞（254.89±17.33 ng/mL）相比，在高表达PD-L1的H460细胞中摄取量显著更高（930.22±11.75 ng/mL，P<0.05）。与对照组（36.43±3.56 μg/g，P<0.05）相比，WL-12@Fe₃O₄组的肿瘤铁水平显著升高（141.02±17.33 μg/g），其他器官无显著差异（P>0.05）。注射探针后，H226和MSTO-211H肿瘤的T2值降低，靶向组的ΔT2值显著高于非靶向组（P<0.05）。ΔT2值在4周内升高，与PD-L1表达密切相关（P<0.05）。
具有MRI功能的靶向PD-L1纳米探针是一种有前景的工具，可用于无创、实时评估MPM中的PD-L1表达。
