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Targeting protumoral tumor-associated macrophages with nanobody-functionalized nanogels through strain promoted azide alkyne cycloaddition ligation

(2018) BIOCONJUGATE CHEMISTRY. 29(7). p.2394-2405
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Abstract
Tumor-associated macrophages (TAMs) with high expression levels of the Macrophage Mannose Receptor (MMR, CD206) exhibit a strong angiogenic and immune suppressive activity. Thus, they are a highly attractive target in cancer immunotherapy, with the aim to modulate their protumoral behavior. Here, we introduce polymer nanogels as potential drug nanocarriers which were site-specifically decorated with a Nanobody (Nb) specific for the MMR. Using azide-functionalized RAFT chain transfer agents, they provide access to amphiphilic reactive ester block copolymers that self assemble into micelles and are afterwards core-cross-linked toward fully hydrophilic nanogels with terminal azide groups on their surface. MMR-targeting Nb can site-selectively be functionalized with one single cyclooctyne moiety by maleimide-cysteine chemistry under mildly reducing conditions which enables successful chemoorthogonal conjugation to the nanogels. The resulting Nb-functionalized nanogels were highly efficient in targeting MMR-expressing cells and TAMs both in vitro and in vivo. We believe that these findings pave the road for targeted eradication or modulation of pro-tumoral MMRhigh TAMs.
Keywords
CATIONIC NANOHYDROGEL PARTICLES, ANTIBODY-FRAGMENTS, COPPER-FREE, POLYMERIC MICELLES, MANNOSE RECEPTOR, MAGIC BULLET, MOUSE MODEL, DELIVERY, CANCER, INFLAMMATION

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MLA
Nuhn, Lutz, et al. “Targeting Protumoral Tumor-Associated Macrophages with Nanobody-Functionalized Nanogels through Strain Promoted Azide Alkyne Cycloaddition Ligation.” BIOCONJUGATE CHEMISTRY, vol. 29, no. 7, 2018, pp. 2394–405, doi:10.1021/acs.bioconjchem.8b00319.
APA
Nuhn, L., Bolli, E., Massa, S., Vandenberghe, I., Movahedi, K., Devreese, B., … De Geest, B. (2018). Targeting protumoral tumor-associated macrophages with nanobody-functionalized nanogels through strain promoted azide alkyne cycloaddition ligation. BIOCONJUGATE CHEMISTRY, 29(7), 2394–2405. https://doi.org/10.1021/acs.bioconjchem.8b00319
Chicago author-date
Nuhn, Lutz, Evangelia Bolli, Sam Massa, Isabel Vandenberghe, Kiavash Movahedi, Bart Devreese, Jo A Van Ginderachter, and Bruno De Geest. 2018. “Targeting Protumoral Tumor-Associated Macrophages with Nanobody-Functionalized Nanogels through Strain Promoted Azide Alkyne Cycloaddition Ligation.” BIOCONJUGATE CHEMISTRY 29 (7): 2394–2405. https://doi.org/10.1021/acs.bioconjchem.8b00319.
Chicago author-date (all authors)
Nuhn, Lutz, Evangelia Bolli, Sam Massa, Isabel Vandenberghe, Kiavash Movahedi, Bart Devreese, Jo A Van Ginderachter, and Bruno De Geest. 2018. “Targeting Protumoral Tumor-Associated Macrophages with Nanobody-Functionalized Nanogels through Strain Promoted Azide Alkyne Cycloaddition Ligation.” BIOCONJUGATE CHEMISTRY 29 (7): 2394–2405. doi:10.1021/acs.bioconjchem.8b00319.
Vancouver
1.
Nuhn L, Bolli E, Massa S, Vandenberghe I, Movahedi K, Devreese B, et al. Targeting protumoral tumor-associated macrophages with nanobody-functionalized nanogels through strain promoted azide alkyne cycloaddition ligation. BIOCONJUGATE CHEMISTRY. 2018;29(7):2394–405.
IEEE
[1]
L. Nuhn et al., “Targeting protumoral tumor-associated macrophages with nanobody-functionalized nanogels through strain promoted azide alkyne cycloaddition ligation,” BIOCONJUGATE CHEMISTRY, vol. 29, no. 7, pp. 2394–2405, 2018.
@article{8605914,
  abstract     = {{Tumor-associated macrophages (TAMs) with high expression levels of the Macrophage Mannose Receptor (MMR, CD206) exhibit a strong angiogenic and immune suppressive activity. Thus, they are a highly attractive target in cancer immunotherapy, with the aim to modulate their protumoral behavior. Here, we introduce polymer nanogels as potential drug nanocarriers which were site-specifically decorated with a Nanobody (Nb) specific for the MMR. Using azide-functionalized RAFT chain transfer agents, they provide access to amphiphilic reactive ester block copolymers that self assemble into micelles and are afterwards core-cross-linked toward fully hydrophilic nanogels with terminal azide groups on their surface. MMR-targeting Nb can site-selectively be functionalized with one single cyclooctyne moiety by maleimide-cysteine chemistry under mildly reducing conditions which enables successful chemoorthogonal conjugation to the nanogels. The resulting Nb-functionalized nanogels were highly efficient in targeting MMR-expressing cells and TAMs both in vitro and in vivo. We believe that these findings pave the road for targeted eradication or modulation of pro-tumoral MMRhigh TAMs.}},
  author       = {{Nuhn, Lutz and Bolli, Evangelia and Massa, Sam and Vandenberghe, Isabel and Movahedi, Kiavash and Devreese, Bart and Van Ginderachter, Jo A and De Geest, Bruno}},
  issn         = {{1043-1802}},
  journal      = {{BIOCONJUGATE CHEMISTRY}},
  keywords     = {{CATIONIC NANOHYDROGEL PARTICLES,ANTIBODY-FRAGMENTS,COPPER-FREE,POLYMERIC MICELLES,MANNOSE RECEPTOR,MAGIC BULLET,MOUSE MODEL,DELIVERY,CANCER,INFLAMMATION}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{2394--2405}},
  title        = {{Targeting protumoral tumor-associated macrophages with nanobody-functionalized nanogels through strain promoted azide alkyne cycloaddition ligation}},
  url          = {{http://dx.doi.org/10.1021/acs.bioconjchem.8b00319}},
  volume       = {{29}},
  year         = {{2018}},
}

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