An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model
A combination therapy using Prussian blue nanoparticles (PBNP) as photothermal therapy (PTT) agents coated with CpG oligodeoxynucleotides, an immunologic adjuvant, as a nanoimmunotherapy (CpG‐PBNP‐PTT) for neuroblastoma (NB) is described. NB driven by MYCN amplification confers high risk and correla...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2021-08-01
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| Series: | Advanced NanoBiomed Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/anbr.202100021 |
| _version_ | 1818355603963117568 |
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| author | Anshi Shukla Juliana Cano-Mejia Jaclyn Andricovich Rachel A. Burga Elizabeth E. Sweeney Rohan Fernandes |
| author_facet | Anshi Shukla Juliana Cano-Mejia Jaclyn Andricovich Rachel A. Burga Elizabeth E. Sweeney Rohan Fernandes |
| author_sort | Anshi Shukla |
| collection | DOAJ |
| description | A combination therapy using Prussian blue nanoparticles (PBNP) as photothermal therapy (PTT) agents coated with CpG oligodeoxynucleotides, an immunologic adjuvant, as a nanoimmunotherapy (CpG‐PBNP‐PTT) for neuroblastoma (NB) is described. NB driven by MYCN amplification confers high risk and correlates with a dismal prognosis, accounting for the majority of NB‐related mortality. The efficacy of the CpG‐PBNP‐PTT nanoimmunotherapy in a clinically relevant, TH‐MYCN murine NB model (9464D) overexpressing MYCN is tested. When administered to 9464D NB cells in vitro, CpG‐PBNP‐PTT triggers thermal dose‐dependent immunogenic cell death and tumor cell priming for immune recognition in vitro, measured by the expression of specific costimulatory and antigen‐presenting molecules. In vivo, intratumorally administered CpG‐PBNP‐PTT generates complete tumor regression and significantly higher long‐term survival compared to controls. Furthermore, CpG‐PBNP‐PTT‐treated mice reject tumor rechallenge. Ex vivo studies confirm these therapeutic responses result from the generation of robust T cell‐mediated immunological memory. Consequently, in a synchronous 9464D tumor model, CpG‐PBNP‐PTT induces complete tumor regression on the treated flank and significantly slows tumor progression on the untreated flank, improving animal survival. These findings demonstrate that localized administration of the CpG‐PBNP‐PTT nanoimmunotherapy drives potent systemic T cell responses in solid tumors such as NB and therefore has therapeutic implications for NB. |
| first_indexed | 2024-12-13T19:43:57Z |
| format | Article |
| id | doaj.art-5cf7b1bafd3f4d918519ba149b88428c |
| institution | Directory Open Access Journal |
| issn | 2699-9307 |
| language | English |
| last_indexed | 2024-12-13T19:43:57Z |
| publishDate | 2021-08-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced NanoBiomed Research |
| spelling | doaj.art-5cf7b1bafd3f4d918519ba149b88428c2022-12-21T23:33:37ZengWiley-VCHAdvanced NanoBiomed Research2699-93072021-08-0118n/an/a10.1002/anbr.202100021An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma ModelAnshi Shukla0Juliana Cano-Mejia1Jaclyn Andricovich2Rachel A. Burga3Elizabeth E. Sweeney4Rohan Fernandes5The George Washington Cancer Center The George Washington University 800 22nd St NW, Science and Engineering Hall 8th Floor Washington DC 20052 USAThe George Washington Cancer Center The George Washington University 800 22nd St NW, Science and Engineering Hall 8th Floor Washington DC 20052 USAThe George Washington Cancer Center The George Washington University 800 22nd St NW, Science and Engineering Hall 8th Floor Washington DC 20052 USAThe George Washington Cancer Center The George Washington University 800 22nd St NW, Science and Engineering Hall 8th Floor Washington DC 20052 USAThe George Washington Cancer Center The George Washington University 800 22nd St NW, Science and Engineering Hall 8th Floor Washington DC 20052 USAThe George Washington Cancer Center The George Washington University 800 22nd St NW, Science and Engineering Hall 8th Floor Washington DC 20052 USAA combination therapy using Prussian blue nanoparticles (PBNP) as photothermal therapy (PTT) agents coated with CpG oligodeoxynucleotides, an immunologic adjuvant, as a nanoimmunotherapy (CpG‐PBNP‐PTT) for neuroblastoma (NB) is described. NB driven by MYCN amplification confers high risk and correlates with a dismal prognosis, accounting for the majority of NB‐related mortality. The efficacy of the CpG‐PBNP‐PTT nanoimmunotherapy in a clinically relevant, TH‐MYCN murine NB model (9464D) overexpressing MYCN is tested. When administered to 9464D NB cells in vitro, CpG‐PBNP‐PTT triggers thermal dose‐dependent immunogenic cell death and tumor cell priming for immune recognition in vitro, measured by the expression of specific costimulatory and antigen‐presenting molecules. In vivo, intratumorally administered CpG‐PBNP‐PTT generates complete tumor regression and significantly higher long‐term survival compared to controls. Furthermore, CpG‐PBNP‐PTT‐treated mice reject tumor rechallenge. Ex vivo studies confirm these therapeutic responses result from the generation of robust T cell‐mediated immunological memory. Consequently, in a synchronous 9464D tumor model, CpG‐PBNP‐PTT induces complete tumor regression on the treated flank and significantly slows tumor progression on the untreated flank, improving animal survival. These findings demonstrate that localized administration of the CpG‐PBNP‐PTT nanoimmunotherapy drives potent systemic T cell responses in solid tumors such as NB and therefore has therapeutic implications for NB.https://doi.org/10.1002/anbr.202100021abscopal effectCpG oligodeoxynucleotidesMYCN amplificationnanoimmunotherapyneuroblastomaphotothermal therapy |
| spellingShingle | Anshi Shukla Juliana Cano-Mejia Jaclyn Andricovich Rachel A. Burga Elizabeth E. Sweeney Rohan Fernandes An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model Advanced NanoBiomed Research abscopal effect CpG oligodeoxynucleotides MYCN amplification nanoimmunotherapy neuroblastoma photothermal therapy |
| title | An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model |
| title_full | An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model |
| title_fullStr | An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model |
| title_full_unstemmed | An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model |
| title_short | An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model |
| title_sort | engineered prussian blue nanoparticles based nanoimmunotherapy elicits robust and persistent immunological memory in a th mycn neuroblastoma model |
| topic | abscopal effect CpG oligodeoxynucleotides MYCN amplification nanoimmunotherapy neuroblastoma photothermal therapy |
| url | https://doi.org/10.1002/anbr.202100021 |
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