Manganese-doped nanotheranostic system for MRI-guided photothermal therapy of malignant pleural mesothelioma: in vivo study

Our plain-English summary of Manganese-doped nanotheranostic system for MRI-guided photothermal therapy of malignant pleural mesothelioma: in vivo study, by L. Lei, H. Zi, S. Kang, et al (Frontiers in Chemistry, 2025).

The study

• Authors: L. Lei, H. Zi, S. Kang, H. Duan, Z. Zhang, C. Gao, R. Xu, D. Han
• Journal: Frontiers in Chemistry
• Published: 2025;13:1659283
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Magnetic Resonance Imaging (MRI)-guided photothermal therapy (PTT) holds significant promise for the treatment of solid tumors, however, its diagnostic and therapeutic efficacy in malignant pleural mesothelioma (MPM) remains underexplored. To address the limitations of traditional gadolinium (Gd)-based MRI contrast agents, such as intolerance in patients with renal insufficiency and T1 signal attenuation at high field strengths, as well as oxidative stress damage caused by manganese ion leakage from manganese-based materials, this study aims to develop highly chelated and stable manganese polydopamine (Mn-PDA) multifunctional nanoprobes for MRI monitoring and PTT treatment of MPM.

Methods: Mn2+ and dopamine were chelated into Mn-PDA NP nanospheres in an ethanol-water system. The physicochemical properties were characterized using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), zeta potential, Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Photoelectron Spectroscopy (XPS), and Electron Paramagnetic Resonance (EPR). The photothermal performance under 808 nm laser irradiation was also evaluated. The MRI imaging performance (longitudinal/transverse relaxation rates, r1/r2) and manganese ion deposition quantification of Mn-PDA NPs were evaluated in vitro and in vivo at 3.0 T MR scanner. Additionally, the PTT efficacy of Mn-PDA NPs was evaluated in MSTO-211H cells and xenograft tumor models. Biocompatibility was assessed through H&E staining of major organs and blood biochemical analyses.

Results: Mn-PDA NPs exhibited a spherical morphology with uniform size (~200 nm), along with high photothermal conversion efficiency, favorable T1-weighted MRI contrast enhancement and low cytotoxicity. At 8 hours post-injection in vivo, Mn-PDA NPs resulted in a 42.9% enhancement in T1-weighted MRI signals within MPM tumors, accompanied by specific tumor accumulation. Under 808 nm laser irradiation, Mn-PDA NPs inhibited MPM tumor growth, as evidenced by reduced tumor volume, expanded areas of tumor necrosis (H&E staining), and downregulated Ki-67 expression. Moreover, stable body weight, normal histological features of major organs, and unaltered blood biochemical parameters were observed in the animals.

Discussion: These findings indicate that Mn-PDA NPs are effective dual-functional agents, serving as both MRI contrast agents and photothermal therapeutics. They exhibit good tumor targeting ability, excellent imaging performance, potent therapeutic efficacy, and high biosafety, thereby offering a promising therapeutic strategy for MPM management.

Copyright © 2025 Lei, Zi, Kang, Duan, Zhang, Gao, Xu and Han.

In plain English

This laboratory and animal study did not involve people or asbestos exposure. The authors made manganese-containing polydopamine nanoparticles (Mn-PDA NPs, average diameter 210.3 nm). The particles were designed to show up on MRI and to heat tumors under 808 nm laser light. They were tested on a human biphasic malignant pleural mesothelioma cell line (MSTO-211H), on a mesothelial cell line, and on nude mice carrying these tumors under the skin. Without laser light, more than 80.0% of cells in both cell lines survived, even at 400 μg/mL. With laser light, survival of mesothelioma cells given Mn-PDA NPs fell to 19.7%. In mice, a tumor MRI measure called the T1 time fell by 42.9% at 8 hours after injection; the authors linked this to a brighter MRI signal. Manganese also built up in the liver, heart, lung and other organs. With the laser, tumors in the Mn-PDA group reached 48.9 °C and showed the strongest growth inhibition, but MRI still showed traces of remaining tumor. Organ tissue showed no abnormalities, and blood tests stayed within normal ranges. The authors concluded that the system showed potential for treating biphasic MPM. They noted that long-term toxicity data are lacking.

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 study: making the nanoparticles, cell-culture experiments, and an animal experiment in mice with human mesothelioma tumors grown under the skin
• Who was studied: Human biphasic malignant pleural mesothelioma cells (MSTO-211H) and immortalized mesothelial cells (MET-5A) in culture. Female BALB/c nude mice, aged 4 to 6 weeks, injected under the skin of the right armpit with MSTO-211H cells, at Kunming Medical University, China. Thirty-six tumor-bearing mice were divided into four treatment groups.
• Exposure: No asbestos exposure was studied. The experimental treatment was Mn-PDA nanoparticles (150 μL at 10 mg/kg, into a vein), followed 8 hours later in laser groups by 808 nm laser light (1 W/cm2, 5 minutes) on the tumor, repeated every 2 days over 14 days. Comparison groups received saline, saline plus laser, or manganese-free DOPA nanoparticles plus laser.
• Main results:
  • The nanoparticles formed spheres with an average diameter of 210.3 ± 18.4 nm.
  • The nanoparticles had an MRI relaxivity (r1) of 9.05 mM−1s−1 on a 3.0 T scanner.
  • Without laser light, more than 80.0% of cells in both cell lines (MeT-5A and MSTO-211H) survived, even at 400 μg/mL of Mn-PDA NPs.
  • With laser light, survival of MSTO-211H mesothelioma cells treated with Mn-PDA NPs dropped to 19.7% ± 1.1%, from 95.5% ± 2.4% in non-irradiated controls.
  • With laser light, survival of MSTO-211H cells treated with manganese-free DOPA nanoparticles was reduced to 52.5% ± 1.2%.
  • In tumor-bearing mice, tumor T1 time fell from 1,293 ± 62.6 ms before injection to 737 ± 82.6 ms at 8 hours after injection of Mn-PDA NPs, a 42.9% ± 4.1% reduction. The authors said this corresponds to an increase in T1-weighted MRI signal.
  • At 8 hours, tumor manganese in the saline control group was 0.31 ± 0.03 mg/kg.
  • At 8 hours, tumor manganese in the Mn-PDA NPs group was 1.12 ± 0.07 mg/kg, which the authors reported as significantly higher than in the saline group.
  • Manganese accumulation was also observed in other organs of the Mn-PDA NPs group, including heart (1.07 ± 0.09 mg/kg) and liver (1.27 ± 0.11 mg/kg).
  • Manganese in the lung of the Mn-PDA NPs group was 1.08 ± 0.1 mg/kg.
  • After 5 minutes of laser light, tumors in Mn-PDA NPs-treated mice reached 48.9 °C (a rise of about 22.4 °C). Tumors in the DOPA NPs group reached 42.5 °C, and in saline-treated mice rose about 6.0 °C.
  • The Mn-PDA NPs plus laser group showed the strongest tumor growth inhibition of the four groups.
  • Although tumors in the Mn-PDA NPs plus laser group appeared almost completely resolved, MRI still showed trace residual tumor tissue in the deep layers under the skin and in the chest wall muscle.
  • Ki-67 staining, a marker of cell growth, was markedly reduced in tumors from the Mn-PDA NPs plus laser group compared with controls.
  • Tissue staining of the heart, liver, spleen, lung and kidney showed no abnormalities in any group, and blood liver, kidney and heart markers stayed within normal reference ranges.
• The authors' conclusion: The authors concluded that the nanoparticles, combined with laser light, suppressed tumor growth in biphasic MPM models without significant whole-body toxicity. They said this shows the potential of a combined diagnostic and treatment nanosystem for biphasic MPM.
• Limitations the authors state:
  • Long-term toxicology data are lacking, as are animal models that closely mimic humans.
  • Clinical use is delayed by potential toxicity risks, especially free manganese building up in nerve cells and possibly damaging them.
  • Future work needs to improve how well the nanoparticles are delivered and to monitor how they are broken down in the body.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Oxidative Stress, Transmission Electron Microscopy (TEM), Infrared Spectroscopy (IR), Deposition, Necrosis, Ki-67.

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