Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells

An in vitro study

Emanuela Cova, Laura Pandolfi, Miriam Colombo, Vanessa Frangipane, Simona Inghilleri, Monica Morosini, Simona Mrakic-Sposta, Sarah Moretti, Manuela Monti, Ymera Pignochino, Silvia Benvenuti, Davide Prosperi, Giulia Stella, Patrizia Morbini, Federica Meloni

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)773-785
Number of pages13
JournalInternational Journal of Nanomedicine
Volume14
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Pemetrexed
Nanoparticles
Gold
Cells
Cell Line
Flow cytometry
Flow Cytometry
In Vitro Techniques
Malignant Mesothelioma
Toxicity
Assays
Cell Cycle

Keywords

  • Gold nanoparticles
  • Intrapleural delivery
  • Mesothelioma
  • Nanodrug delivery
  • Pemetrexed

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells : An in vitro study. / Cova, Emanuela; Pandolfi, Laura; Colombo, Miriam; Frangipane, Vanessa; Inghilleri, Simona; Morosini, Monica; Mrakic-Sposta, Simona; Moretti, Sarah; Monti, Manuela; Pignochino, Ymera; Benvenuti, Silvia; Prosperi, Davide; Stella, Giulia; Morbini, Patrizia; Meloni, Federica.

In: International Journal of Nanomedicine, Vol. 14, 01.01.2019, p. 773-785.

Research output: Contribution to journalArticle

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T2 - An in vitro study

AU - Cova, Emanuela

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AU - Colombo, Miriam

AU - Frangipane, Vanessa

AU - Inghilleri, Simona

AU - Morosini, Monica

AU - Mrakic-Sposta, Simona

AU - Moretti, Sarah

AU - Monti, Manuela

AU - Pignochino, Ymera

AU - Benvenuti, Silvia

AU - Prosperi, Davide

AU - Stella, Giulia

AU - Morbini, Patrizia

AU - Meloni, Federica

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