Intrapleural Trastuzumab Therapy for Malignant Pleural Effusion from HER2 Overexpression in Metastatic Gastric Cancer

Orlandi, Elena; Mordenti, Patrizia; Zangrandi, Adriano; Cavanna, Luigi

doi:10.1159/000437136

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…Furthermore, CD146 targeting offers the possibility of new approaches that could be translated to the treatment of other cancers or metastasis affecting the pleural or peritoneal space. 41 For personal use only.…”

Section: Discussionmentioning

confidence: 99%

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Cova

Pandolfi

Colombo

et al. 2019

IJN

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PurposeMalignant 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.MethodsMPM 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).ResultsGNP-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.ConclusionGNP-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.

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Section: Discussionmentioning

confidence: 99%

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Cova

Pandolfi

Colombo

et al. 2019

IJN

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: In-vitro study

Stella¹,

Cova²,

Inghilleri³

et al. 2015

11.2 Pleural and Mediastinal Malignancies

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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.

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Trastuzumab drug delivery systems for magnetic resonance imaging detection

Aebisher

Bartusik

2018

Design of Nanostructures for Theranostics Applications

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Intrapleural Trastuzumab Therapy for Malignant Pleural Effusion from HER2 Overexpression in Metastatic Gastric Cancer

Cited by 3 publications

References 14 publications

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: In-vitro study

Trastuzumab drug delivery systems for magnetic resonance imaging detection

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