{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:09:18Z","timestamp":1761102558283,"version":"3.41.2"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A PD-L1-binding peptide (WL-12) was conjugated with superparamagnetic iron oxide nanoparticles (SPIONs) to create the nanoprobe WL-12@Fe\u2083O\u2084. The nanoprobe\u2019s stability, biotoxicity, targeting ability, and <jats:italic>in vivo<\/jats:italic> magnetic resonance (MR) imaging effects were assessed and compared to non-targeted Fe\u2083O\u2084 nanoparticles. \u0394T2 values and PD-L1 expression were measured in H226 and MSTO-211H tumor tissues over 4 weeks to analyze correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The WL-12@Fe\u2083O\u2084 nanoprobe demonstrated uniform distribution and a spherical shape, with a larger size (43.82\u00a0nm) and lower surface potential (\u22129.34 \u00b1 0.54\u00a0mV) compared to Fe\u2083O\u2084 (32.67\u00a0nm, \u221220.20 \u00b1 0.88\u00a0mV, <jats:italic>P<\/jats:italic> &amp;lt; 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with Fe<jats:sub>3<\/jats:sub>O<jats:sub>4.<\/jats:sub> It was well dispersed in serum and saline and showed no cytotoxicity or organ damage <jats:italic>in vivo<\/jats:italic>. 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 \u00b1 11.75\u00a0ng\/mL) compared to low PD-L1-expressing A549 cells (254.89 \u00b1 17.33\u00a0ng\/mL, <jats:italic>P<\/jats:italic> &amp;lt; 0.05). Tumor iron levels in the WL-12@Fe\u2083O\u2084 group were significantly elevated (141.02 \u00b1 17.33\u00a0\u03bcg\/g) compared to controls (36.43 \u00b1 3.56\u00a0\u03bcg\/g, <jats:italic>P<\/jats:italic> &amp;lt; 0.05), with no significant differences in other organs (<jats:italic>P<\/jats:italic> &amp;gt; 0.05). The T2 values of H226 and MSTO-211H tumors decreased after probe injection, with \u0394T2 values significantly higher in the targeted group than the nontargeted group (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). \u0394T2 values increased over 4\u00a0weeks, correlating strongly with PD-L1 expression (<jats:italic>P<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fchem.2024.1508912","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T04:24:20Z","timestamp":1733113460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Detection of PD-L1 expression levels in malignant pleural mesothelioma with a targeted MRI nanoprobe in vivo"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhenghua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lichang","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/s0140-6736(20)32714-8","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743):a multicentre, randomised, open-label, phase 3 trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e001156","DOI":"10.1136\/jitc-2020-001156","article-title":"Nuclear imaging-guided PD-L1 blockade therapy increases effectiveness of cancer immunotherapy","volume":"8","author":"Gao","year":"2020","journal-title":"J. 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