Detection of PD-L1 expression levels in malignant pleural mesothelioma with a targeted MRI nanoprobe in vivo

Our plain-English summary of Detection of PD-L1 expression levels in malignant pleural mesothelioma with a targeted MRI nanoprobe in vivo, by Z. Zhang, Y. Tian, W. Gao, et al (Frontiers in Chemistry, 2024).

The study

• Authors: Z. Zhang, Y. Tian, W. Gao, Y. Hu, L. Luo, L. Lei, S. Shen, D. Han
• Journal: Frontiers in Chemistry
• Published: 2024;12:1508912
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: 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).

Methods: 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 in vivo 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.

Results: 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, P < 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with Fe3O4. It was well dispersed in serum and saline and showed no cytotoxicity or organ damage in vivo. 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, P < 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, P < 0.05), with no significant differences in other organs (P > 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 (P < 0.05). ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression (P < 0.05).

Conclusion: The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.

Copyright © 2024 Zhang, Tian, Gao, Hu, Luo, Lei, Shen and Han.

In plain English

This was a laboratory and animal experiment. The authors attached a peptide called WL-12, which binds the protein PD-L1, to iron oxide nanoparticles to make an MRI probe. They compared it with untargeted iron oxide particles. They tested it on human malignant pleural mesothelioma cell lines (H226, epithelial-type; MSTO-211H, biphasic), on two lung cancer cell lines, and in female nude mice carrying tumors grown under the skin. Asbestos exposure was not studied. Cell survival stayed above 90%, and no organ damage was seen on microscopy. Cells with high PD-L1 (H460) took up more iron than cells with low PD-L1 (A549). Tumors in mice given the targeted probe held more iron than tumors given untargeted particles. The targeted probe also produced larger MRI signal changes (ΔT2) in both tumor types. Over four weeks, ΔT2 and PD-L1 expression both rose, with a correlation of R = 0.97. The authors concluded that the probe is a promising tool for noninvasive assessment of PD-L1 in mesothelioma. They noted that the tumors were not grown in the chest.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (cell culture) and animal experiment developing and testing a PD-L1-targeted MRI nanoprobe
• Who was studied: Human malignant pleural mesothelioma cell lines H226 (epithelial-type) and MSTO-211H (biphasic), plus lung cancer cell lines A549 and H460. Animal work used female BALB/c nude mice, four to six weeks old, with H226 or MSTO-211H tumors injected under the skin of the right armpit. The article reports 5 mice per group (20 in total) for the imaging comparison and 20 per group (40 in total) for the four-week study. The work was done at Kunming Medical University, China.
• Exposure: Not an asbestos exposure study. The 'exposure' was the WL-12-coated iron oxide nanoprobe (WL-12@Fe3O4) compared with uncoated Fe3O4 nanoparticles, given as 100 µL at 1 mg/mL into the tail vein.
• Main results:
  • The targeted nanoprobe had an average size of 43.82 nm, compared with 32.67 nm for the plain Fe3O4 particles. Its surface charge was −9.34 ± 0.54 mV, compared with −20.20 ± 0.88 mV for Fe3O4 (P < 0.05).
  • In H226 and MSTO-211H cells exposed to the nanoparticles at 0 to 200 μg/mL for 24 hours, cell viability stayed above 90%. Microscopy of the brain, heart, lungs, liver, spleen and kidneys of injected mice showed no necrosis, fibrosis or other pathological changes.
  • With the targeted probe, blue (iron) particle deposits were seen on the mesothelioma cells, particularly MSTO-211H. No visible deposits were seen with the untargeted Fe3O4 particles.
  • Iron concentration was 930.22 ± 11.75 ng/mL in high-PD-L1 H460 lung cancer cells, compared with 254.89 ± 17.33 ng/mL in low-PD-L1 A549 cells (P < 0.05).
  • In tumor-bearing mice, tumor iron was 141.02 ± 3.82 μg/g with the targeted probe, compared with 36.43 ± 3.56 μg/g with untargeted Fe3O4 (P < 0.05). Other organs showed no statistically significant differences between the two groups (P > 0.05).
  • The MRI signal change (ΔT2) was larger with the targeted probe than with the untargeted particles (P < 0.05):
• H226 tumors: 12.38 ± 1.05, compared with 8.04 ± 0.93.
• MSTO-211H tumors: 16.26 ± 2.02, compared with 11.38 ± 1.16.
  The units are printed as 'm'. ΔT2 was also larger in MSTO-211H tumors than in H226 tumors (P < 0.05).
  • Over 1, 2, 3 and 4 weeks of tumor growth, both ΔT2 and PD-L1 expression in the tumor tissue increased gradually. ΔT2 and PD-L1 expression were strongly positively correlated (R = 0.97, P < 0.05).
• The authors' conclusion: The authors concluded that the PD-L1-targeted nanoprobe used with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in malignant pleural mesothelioma.
• Limitations the authors state:
  • Tumors were transplanted under the skin rather than into the chest. The authors state that a model with tumors grown in the chest is needed to study PD-L1 changes in the mesothelioma tumor environment.
  • How the nanoprobe is distributed in the body over time needs further exploration.
  • Organ safety was judged by microscopy only. Further functional assessments are needed to fully evaluate changes in organ function.

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, checkpoint inhibitors, A549 Cells.

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