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Int J Nanomedicine. 2019 Jan 23;14:773-785. doi: 10.2147/IJN.S186344. eCollection 2019.

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study.

Author information

1
Clinic of Lung Diseases, IRCCS Foundation Policlinico San Matteo, Pavia, Italy, e.cova@smatteo.pv.it.
2
Deparment of Biotechnology and Bioscience, University of Milano - Bicocca, Milan, Italy, miriam.colombo@unimib.it.
3
National Council of Research, Institute of Bioimaging and Molecular Physiology, Segrate, Milan, Italy.
4
Laboratory of Biotechnology, Research Center of Rigenerative Medicine, IRCCS Foundation Policlinico San Matteo, Pavia, Italy.
5
Experimental Clinical Molecular Oncology, IRCCS Candiolo Cancer Institute-FPO, Candiolo, Turin, Italy.
6
Laboratory of Nanomedicine, Clinical Institute of Maugeri, S.p.A., Pavia, Italy.
7
Department of Molecular Medicine, Pathology Unit, IRCCS Foundation Policlinico San Matteo, Pavia, Italy.
8
Department of Internal Medicine, Pneumology Unit, University of Pavia, Pavia, Italy.

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.

KEYWORDS:

gold nanoparticles; intrapleural delivery; mesothelioma; nanodrug delivery; pemetrexed

PMID:
30774332
PMCID:
PMC6361319
DOI:
10.2147/IJN.S186344
[Indexed for MEDLINE]
Free PMC Article

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