DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells
IntroductionThe functionalization of nanoparticles (NPs) with an antiCD19 targeting mechanism represents a promising approach for the selective delivery of drugs and nucleic acids into normal and tumor B cells. This strategy has the advantage of minimizing off-target effects by restricting gene deli...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509322/full |
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| author | Maria Cristina Grimaldi Sara Bozzer Dick J. Sjöström Dick J. Sjöström Linnea I. Andersson Tom Eirik Mollnes Tom Eirik Mollnes Per H. Nilsson Per H. Nilsson Luca De Maso Federico Riccardi Michele Dal Bo Daniele Sblattero Paolo Macor |
| author_facet | Maria Cristina Grimaldi Sara Bozzer Dick J. Sjöström Dick J. Sjöström Linnea I. Andersson Tom Eirik Mollnes Tom Eirik Mollnes Per H. Nilsson Per H. Nilsson Luca De Maso Federico Riccardi Michele Dal Bo Daniele Sblattero Paolo Macor |
| author_sort | Maria Cristina Grimaldi |
| collection | DOAJ |
| description | IntroductionThe functionalization of nanoparticles (NPs) with an antiCD19 targeting mechanism represents a promising approach for the selective delivery of drugs and nucleic acids into normal and tumor B cells. This strategy has the advantage of minimizing off-target effects by restricting gene delivery to the desired cell population. However, the nanoplatform must guarantee both the local production of the protein and the safety of the treatment to allow an effective therapy with reduced systemic toxicity.MethodsIn order to ensure a selective delivery of nucleic acids, we developed poly(lactic-co-glycolic acid) (PLGA)-poly(vinyl alcohol) (PVA) NPs loaded with an Enhanced Green Fluorescent Protein (EGFP)-coding plasmid and covalently coated with antiCD19 recombinant antibody as a targeting mechanism. To assess the functionality of the NPs, physicochemical characterization, safety tests, and transfection assay were employed to evaluate the NPs’ behavior in vitro and in vivo, in a human/zebrafish lymphoma xenograft model.ResultsThe results demonstrated that the PLGA-PVA nanoplatform was capable of efficiently encapsulating and releasing the payload. These nanostructures demonstrated a favorable safety profile, as evidenced by the absence of significant cell cytotoxicity, coagulation activation, complement system activation, and the slight activation of endothelial cells and leukocytes. The targeting mechanism facilitated the interaction of NPs with target cells, thereby enhancing their internalization and subsequent exogenous plasmid DNA (pDNA) translation and protein expression. In the human/zebrafish lymphoma xenograft model, no evidence of toxicity was observed, and targeted NPs demonstrated the capacity to enhance exogenous pDNA expression.ConclusionOur findings provide a rationale for the use of targeted NPs as a DNA delivery system for the local expression of therapeutic proteins. |
| format | Article |
| id | doaj-art-cab2e7acdd54496eb94db7f4dc7aa143 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-cab2e7acdd54496eb94db7f4dc7aa1432025-01-22T07:11:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15093221509322DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cellsMaria Cristina Grimaldi0Sara Bozzer1Dick J. Sjöström2Dick J. Sjöström3Linnea I. Andersson4Tom Eirik Mollnes5Tom Eirik Mollnes6Per H. Nilsson7Per H. Nilsson8Luca De Maso9Federico Riccardi10Michele Dal Bo11Daniele Sblattero12Paolo Macor13Department of Life Sciences, University of Trieste, Trieste, ItalyExperimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, ItalyLinnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, SwedenDepartment of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, SwedenLinnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, SwedenDepartment of Immunology, Oslo University Hospital and University of Oslo, Oslo, NorwayResearch Laboratory, Nordland Hospital, Bodo, NorwayLinnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, SwedenDepartment of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, SwedenDepartment of Life Sciences, University of Trieste, Trieste, ItalyExperimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, ItalyExperimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyIntroductionThe functionalization of nanoparticles (NPs) with an antiCD19 targeting mechanism represents a promising approach for the selective delivery of drugs and nucleic acids into normal and tumor B cells. This strategy has the advantage of minimizing off-target effects by restricting gene delivery to the desired cell population. However, the nanoplatform must guarantee both the local production of the protein and the safety of the treatment to allow an effective therapy with reduced systemic toxicity.MethodsIn order to ensure a selective delivery of nucleic acids, we developed poly(lactic-co-glycolic acid) (PLGA)-poly(vinyl alcohol) (PVA) NPs loaded with an Enhanced Green Fluorescent Protein (EGFP)-coding plasmid and covalently coated with antiCD19 recombinant antibody as a targeting mechanism. To assess the functionality of the NPs, physicochemical characterization, safety tests, and transfection assay were employed to evaluate the NPs’ behavior in vitro and in vivo, in a human/zebrafish lymphoma xenograft model.ResultsThe results demonstrated that the PLGA-PVA nanoplatform was capable of efficiently encapsulating and releasing the payload. These nanostructures demonstrated a favorable safety profile, as evidenced by the absence of significant cell cytotoxicity, coagulation activation, complement system activation, and the slight activation of endothelial cells and leukocytes. The targeting mechanism facilitated the interaction of NPs with target cells, thereby enhancing their internalization and subsequent exogenous plasmid DNA (pDNA) translation and protein expression. In the human/zebrafish lymphoma xenograft model, no evidence of toxicity was observed, and targeted NPs demonstrated the capacity to enhance exogenous pDNA expression.ConclusionOur findings provide a rationale for the use of targeted NPs as a DNA delivery system for the local expression of therapeutic proteins.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509322/fullpolymeric nanoparticlestargetingsafetyin vivo transfectionzebrafish |
| spellingShingle | Maria Cristina Grimaldi Sara Bozzer Dick J. Sjöström Dick J. Sjöström Linnea I. Andersson Tom Eirik Mollnes Tom Eirik Mollnes Per H. Nilsson Per H. Nilsson Luca De Maso Federico Riccardi Michele Dal Bo Daniele Sblattero Paolo Macor DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells Frontiers in Immunology polymeric nanoparticles targeting safety in vivo transfection zebrafish |
| title | DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells |
| title_full | DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells |
| title_fullStr | DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells |
| title_full_unstemmed | DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells |
| title_short | DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells |
| title_sort | dna loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor b cells |
| topic | polymeric nanoparticles targeting safety in vivo transfection zebrafish |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509322/full |
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