The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses
Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which bec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/4/978 |
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| author | Irati Beltrán Hernández Mathieu L. Angelier Tommaso Del Buono D’Ondes Alessia Di Maggio Yingxin Yu Sabrina Oliveira |
| author_facet | Irati Beltrán Hernández Mathieu L. Angelier Tommaso Del Buono D’Ondes Alessia Di Maggio Yingxin Yu Sabrina Oliveira |
| author_sort | Irati Beltrán Hernández |
| collection | DOAJ |
| description | Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro- inflammatory cytokines IL- 1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach. |
| first_indexed | 2024-03-10T20:27:38Z |
| format | Article |
| id | doaj.art-f3432ee29717467190a44194360c8d9e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:27:38Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f3432ee29717467190a44194360c8d9e2023-11-19T21:40:47ZengMDPI AGCancers2072-66942020-04-0112497810.3390/cancers12040978The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune ResponsesIrati Beltrán Hernández0Mathieu L. Angelier1Tommaso Del Buono D’Ondes2Alessia Di Maggio3Yingxin Yu4Sabrina Oliveira5Pharmaceutics, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The NetherlandsPharmaceutics, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The NetherlandsPharmaceutics, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The NetherlandsNanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro- inflammatory cytokines IL- 1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach.https://www.mdpi.com/2072-6694/12/4/978targeted photodynamic therapynanobodiesEGFRDAMPsimmune stimulation |
| spellingShingle | Irati Beltrán Hernández Mathieu L. Angelier Tommaso Del Buono D’Ondes Alessia Di Maggio Yingxin Yu Sabrina Oliveira The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses Cancers targeted photodynamic therapy nanobodies EGFR DAMPs immune stimulation |
| title | The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses |
| title_full | The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses |
| title_fullStr | The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses |
| title_full_unstemmed | The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses |
| title_short | The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses |
| title_sort | potential of nanobody targeted photodynamic therapy to trigger immune responses |
| topic | targeted photodynamic therapy nanobodies EGFR DAMPs immune stimulation |
| url | https://www.mdpi.com/2072-6694/12/4/978 |
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