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Pemetrexed-loadednanoparticlestargeted to malignantpleural mesotheliomacells: an in vitrostudy Emanuela CovaLaura PandolfiMiriam Colombo2019 год

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>
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Аннотация: 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.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).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.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.
Год издания: 2019
Авторы: 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 Maria Stella, Patrizia Morbini, Federica Meloni
Издательство: Dove Medical Press
Источник: International Journal of Nanomedicine
Ключевые слова: Occupational and environmental lung diseases, Graphene and Nanomaterials Applications, Pleural and Pulmonary Diseases
Другие ссылки: International Journal of Nanomedicine (PDF)
International Journal of Nanomedicine (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
BOA (University of Milano-Bicocca) (PDF)
BOA (University of Milano-Bicocca) (HTML)
Institutional Research Information System University of Turin (University of Turin) (PDF)
Institutional Research Information System University of Turin (University of Turin) (HTML)
PubMed Central (HTML)
PubMed (HTML)