PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets
Successful cell targeting depends on the controlled positioning of cell-type-specific antibodies on the nanocarrier’s (NC) surface. Uncontrolled antibody immobilization results in unintended cell uptake due to Fc-mediated cell interaction. Consequently, precise immobilization of the Fc region toward...
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MDPI AG
2022-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/8/1614 |
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| author | Maximilian Brückner Michael Fichter Richard da Costa Marques Katharina Landfester Volker Mailänder |
| author_facet | Maximilian Brückner Michael Fichter Richard da Costa Marques Katharina Landfester Volker Mailänder |
| author_sort | Maximilian Brückner |
| collection | DOAJ |
| description | Successful cell targeting depends on the controlled positioning of cell-type-specific antibodies on the nanocarrier’s (NC) surface. Uncontrolled antibody immobilization results in unintended cell uptake due to Fc-mediated cell interaction. Consequently, precise immobilization of the Fc region towards the nanocarrier surface is needed with the Fab regions staying freely accessible for antigen binding. Moreover, the antibody needs to be a certain distance from the nanocarrier surface, influencing the targeting performance after formation of the biomolecular corona. This can be achieved by using PEG linker molecules. Here we demonstrate cell type-specific targeting for dendritic cells (DC) as cellular key regulators of immune responses. However, to date, dendritic cell targeting experiments using different linker lengths still need to be conducted. Consequently, we focused on the surface modification of nanocarriers with different molecular weight PEG linkers (0.65, 2, and 5 kDa), and their ability to reduce undesired cell uptake, while achieving efficient DC targeting via covalently immobilized antibodies (stealth targeting). Our findings demonstrate that the PEG linker length significantly affects active dendritic cell targeting from cell lines (DC2.4) to primary cells (BMDCs, splenocytic conventional DCs type 1 (cDC1)). While antibody-functionalized nanocarriers with a shorter PEG length (0.65 kDa) showed the best targeting in DC2.4, a longer PEG length (5 kDa) was required to specifically accumulate in BMDCs and splenocytic cDC1. Our study highlights that these crucial aspects must be considered when targeting dendritic cell subsets, which are of great importance in the fields of cancer immunotherapy and vaccine development. |
| first_indexed | 2024-03-09T12:46:40Z |
| format | Article |
| id | doaj.art-3dd97ff2e3d542dc965988ce348d4b99 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:46:40Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3dd97ff2e3d542dc965988ce348d4b992023-11-30T22:11:23ZengMDPI AGPharmaceutics1999-49232022-08-01148161410.3390/pharmaceutics14081614PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell SubsetsMaximilian Brückner0Michael Fichter1Richard da Costa Marques2Katharina Landfester3Volker Mailänder4Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, GermanyMax Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, GermanySuccessful cell targeting depends on the controlled positioning of cell-type-specific antibodies on the nanocarrier’s (NC) surface. Uncontrolled antibody immobilization results in unintended cell uptake due to Fc-mediated cell interaction. Consequently, precise immobilization of the Fc region towards the nanocarrier surface is needed with the Fab regions staying freely accessible for antigen binding. Moreover, the antibody needs to be a certain distance from the nanocarrier surface, influencing the targeting performance after formation of the biomolecular corona. This can be achieved by using PEG linker molecules. Here we demonstrate cell type-specific targeting for dendritic cells (DC) as cellular key regulators of immune responses. However, to date, dendritic cell targeting experiments using different linker lengths still need to be conducted. Consequently, we focused on the surface modification of nanocarriers with different molecular weight PEG linkers (0.65, 2, and 5 kDa), and their ability to reduce undesired cell uptake, while achieving efficient DC targeting via covalently immobilized antibodies (stealth targeting). Our findings demonstrate that the PEG linker length significantly affects active dendritic cell targeting from cell lines (DC2.4) to primary cells (BMDCs, splenocytic conventional DCs type 1 (cDC1)). While antibody-functionalized nanocarriers with a shorter PEG length (0.65 kDa) showed the best targeting in DC2.4, a longer PEG length (5 kDa) was required to specifically accumulate in BMDCs and splenocytic cDC1. Our study highlights that these crucial aspects must be considered when targeting dendritic cell subsets, which are of great importance in the fields of cancer immunotherapy and vaccine development.https://www.mdpi.com/1999-4923/14/8/1614antibody functionalizationnanoparticlesnanovaccinedendritic cell targetingPEG |
| spellingShingle | Maximilian Brückner Michael Fichter Richard da Costa Marques Katharina Landfester Volker Mailänder PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets Pharmaceutics antibody functionalization nanoparticles nanovaccine dendritic cell targeting PEG |
| title | PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets |
| title_full | PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets |
| title_fullStr | PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets |
| title_full_unstemmed | PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets |
| title_short | PEG Spacer Length Substantially Affects Antibody-Based Nanocarrier Targeting of Dendritic Cell Subsets |
| title_sort | peg spacer length substantially affects antibody based nanocarrier targeting of dendritic cell subsets |
| topic | antibody functionalization nanoparticles nanovaccine dendritic cell targeting PEG |
| url | https://www.mdpi.com/1999-4923/14/8/1614 |
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