Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs
The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polyme...
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MDPI AG
2019-01-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/11/1/12 |
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| author | Larissa Gomes dos Reis Wing-Hin Lee Maree Svolos Lyn Margaret Moir Rima Jaber Norbert Windhab Paul Michael Young Daniela Traini |
| author_facet | Larissa Gomes dos Reis Wing-Hin Lee Maree Svolos Lyn Margaret Moir Rima Jaber Norbert Windhab Paul Michael Young Daniela Traini |
| author_sort | Larissa Gomes dos Reis |
| collection | DOAJ |
| description | The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic–co–glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs–DNA–CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%–15%) after 24 h of incubation and increase in autophagy, induced by NPs–DNA–CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs–DNA–CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs. |
| first_indexed | 2024-04-11T11:03:36Z |
| format | Article |
| id | doaj.art-f4af0c2fd0204cd3a9243111e25c87a8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T11:03:36Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f4af0c2fd0204cd3a9243111e25c87a82022-12-22T04:28:29ZengMDPI AGPharmaceutics1999-49232019-01-011111210.3390/pharmaceutics11010012pharmaceutics11010012Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the LungsLarissa Gomes dos Reis0Wing-Hin Lee1Maree Svolos2Lyn Margaret Moir3Rima Jaber4Norbert Windhab5Paul Michael Young6Daniela Traini7Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2037, AustraliaFaculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur-Royal College of Medicine Perak, (UniKL-RCMP), 30450 Ipoh, Perak, MalaysiaRespiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2037, AustraliaRespiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2037, AustraliaEvonik Industries AG, Kirschenallee, 64293 Darmstadt, GermanyEvonik Industries AG, Kirschenallee, 64293 Darmstadt, GermanyRespiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2037, AustraliaRespiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2037, AustraliaThe use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic–co–glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs–DNA–CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%–15%) after 24 h of incubation and increase in autophagy, induced by NPs–DNA–CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs–DNA–CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs.http://www.mdpi.com/1999-4923/11/1/12alveolarbronchialapoptosisautophagygene delivery |
| spellingShingle | Larissa Gomes dos Reis Wing-Hin Lee Maree Svolos Lyn Margaret Moir Rima Jaber Norbert Windhab Paul Michael Young Daniela Traini Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs Pharmaceutics alveolar bronchial apoptosis autophagy gene delivery |
| title | Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs |
| title_full | Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs |
| title_fullStr | Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs |
| title_full_unstemmed | Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs |
| title_short | Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs |
| title_sort | nanotoxicologic effects of plga nanoparticles formulated with a cell penetrating peptide searching for a safe pdna delivery system for the lungs |
| topic | alveolar bronchial apoptosis autophagy gene delivery |
| url | http://www.mdpi.com/1999-4923/11/1/12 |
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