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Updated: Jan 29, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study
Emanuela Cova1, Laura Pandolfi1, Miriam Colombo2
1Clinic of Lung Diseases, IRCCS Foundation Policlinico San Matteo, Pavia, Italy, e.cova@smatteo.pv.it.
Purpose:
Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.
Methods:
MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).
Results:
GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.
Conclusion:
GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.
Insights
Targeted gold nanoparticles loaded with chemotherapy show promise for treating malignant pleural mesothelioma (MPM). This novel approach enhances drug efficacy and reduces toxicity for advanced MPM.
Area of Science:
- Oncology
- Nanomedicine
- Biotechnology
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
- Current therapies like Pemetrexed (Pe) have restricted efficacy.
- Gold nanoparticles (GNPs) offer potential for targeted drug delivery and reduced systemic toxicity.
Purpose of the Study:
- To investigate CD146 as a specific target for engineered Pemetrexed-loaded gold nanoparticles (GNP-HCPe) in MPM.
- To evaluate the effectiveness of GNP-HCPe in inhibiting MPM cell line growth and malignant phenotype.
Main Methods:
- MPM cell lines and patient samples were analyzed for CD146 expression.
- Internalization of anti-CD146 coated GNPs (GNP-HC) by MPM cells was confirmed.
- Effects of GNP-HCPe on cell cycle, viability, clonogenic capacity, ROS production, motility, and apoptosis were assessed.
Main Results:
- GNP-HC were rapidly and selectively internalized by MPM cells.
- GNP-HCPe treatment induced S-phase cell cycle arrest and significantly reduced cell viability and motility compared to Pemetrexed alone.
- Apoptosis and reactive oxygen species (ROS) production were significantly increased, and clonogenic capacity was completely inhibited.
Conclusions:
- GNP-HCPe demonstrates significant in vitro antineoplastic activity against MPM cell lines, outperforming Pemetrexed monotherapy.
- Targeted GNPs offer a promising strategy for localized intrapleural administration, potentially enhancing chemotherapy efficacy while minimizing normal tissue toxicity.
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