Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells
Abstract
Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune disorders. SNAbs However, their use is limited by high development time and monetary cost, manufacturing complexities, suboptimal pharmacokinetics, and availability of disease-specific targets. To address some of these challenges, we developed an entirely synthetic, multivalent, Janus nanotherapeutic platform, called Synthetic Nanoparticle Antibodies (SNAbs). SNAbs, with phage-display-identified cell-targeting ligands on one "face" and Fc-mimicking ligands on the opposite "face", were synthesized using a custom, multistep, solid-phase chemistry method. SNAbs efficiently targeted and depleted myeloid-derived immune-suppressor cells (MDSCs) from mouse-tumor and rat-trauma models, ex vivo. Systemic injection of MDSC-targeting SNAbs efficiently depleted circulating MDSCs in a mouse triple-negative breast cancer model, enabling enhanced T cell and Natural Killer cell infiltration into tumors. Finally, our results demonstrate that SNAbs are a versatile and effective functional alternative to mAbs, with advantages of a plug- and-play, cell-free manufacturing process, and high-throughput screening (HTS)-enabled library of potential targeting ligands.
- Authors:
-
[2];
[1];
[1];
[1];
[1];
[1]
- Georgia Inst. of Technology, Atlanta, GA (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Univ. of Pittsburgh, PA (United States)
- Emory Univ., Atlanta, GA (United States); Atlanta VA Medical Center, Decatur, GA (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; Georgia Institute of Technology; National Science Foundation (NSF); National Institutes of Health (NIH)
- OSTI Identifier:
- 1798050
- Grant/Contract Number:
- AC02-06CH11357; 12456J4; 1255d06; ECCS-2025462; R01-GM123169; TG-MCB130173
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nano Letters
- Additional Journal Information:
- Journal Volume: 21; Journal Issue: 1; Journal ID: ISSN 1530-6984
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Janus nanoparticle; antibody-dependent cellular responses; immunotherapy; monoclonal antibody; myeloid-derived suppressor cell
Citation Formats
Liu, Jiaying, Toy, Randall, Vantucci, Casey, Pradhan, Pallab, Zhang, Zijian, Kuo, Katie M., Kubelick, Kelsey P., Huo, Da, Wen, Jianguo, Kim, Jinhwan, Lyu, Zhiheng, Dhal, Simran, Atalis, Alexandra, Ghosh-Choudhary, Shohini K., Devereaux, Emily J., Gumbart, James C., Xia, Younan, Emelianov, Stanislav Y., Willett, Nick J., and Roy, Krishnendu. Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells. United States: N. p., 2021.
Web. doi:10.1021/acs.nanolett.0c04833.
Liu, Jiaying, Toy, Randall, Vantucci, Casey, Pradhan, Pallab, Zhang, Zijian, Kuo, Katie M., Kubelick, Kelsey P., Huo, Da, Wen, Jianguo, Kim, Jinhwan, Lyu, Zhiheng, Dhal, Simran, Atalis, Alexandra, Ghosh-Choudhary, Shohini K., Devereaux, Emily J., Gumbart, James C., Xia, Younan, Emelianov, Stanislav Y., Willett, Nick J., & Roy, Krishnendu. Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells. United States. https://doi.org/10.1021/acs.nanolett.0c04833
Liu, Jiaying, Toy, Randall, Vantucci, Casey, Pradhan, Pallab, Zhang, Zijian, Kuo, Katie M., Kubelick, Kelsey P., Huo, Da, Wen, Jianguo, Kim, Jinhwan, Lyu, Zhiheng, Dhal, Simran, Atalis, Alexandra, Ghosh-Choudhary, Shohini K., Devereaux, Emily J., Gumbart, James C., Xia, Younan, Emelianov, Stanislav Y., Willett, Nick J., and Roy, Krishnendu. Mon .
"Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells". United States. https://doi.org/10.1021/acs.nanolett.0c04833. https://www.osti.gov/servlets/purl/1798050.
@article{osti_1798050,
title = {Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells},
author = {Liu, Jiaying and Toy, Randall and Vantucci, Casey and Pradhan, Pallab and Zhang, Zijian and Kuo, Katie M. and Kubelick, Kelsey P. and Huo, Da and Wen, Jianguo and Kim, Jinhwan and Lyu, Zhiheng and Dhal, Simran and Atalis, Alexandra and Ghosh-Choudhary, Shohini K. and Devereaux, Emily J. and Gumbart, James C. and Xia, Younan and Emelianov, Stanislav Y. and Willett, Nick J. and Roy, Krishnendu},
abstractNote = {Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune disorders. SNAbs However, their use is limited by high development time and monetary cost, manufacturing complexities, suboptimal pharmacokinetics, and availability of disease-specific targets. To address some of these challenges, we developed an entirely synthetic, multivalent, Janus nanotherapeutic platform, called Synthetic Nanoparticle Antibodies (SNAbs). SNAbs, with phage-display-identified cell-targeting ligands on one "face" and Fc-mimicking ligands on the opposite "face", were synthesized using a custom, multistep, solid-phase chemistry method. SNAbs efficiently targeted and depleted myeloid-derived immune-suppressor cells (MDSCs) from mouse-tumor and rat-trauma models, ex vivo. Systemic injection of MDSC-targeting SNAbs efficiently depleted circulating MDSCs in a mouse triple-negative breast cancer model, enabling enhanced T cell and Natural Killer cell infiltration into tumors. Finally, our results demonstrate that SNAbs are a versatile and effective functional alternative to mAbs, with advantages of a plug- and-play, cell-free manufacturing process, and high-throughput screening (HTS)-enabled library of potential targeting ligands.},
doi = {10.1021/acs.nanolett.0c04833},
journal = {Nano Letters},
number = 1,
volume = 21,
place = {United States},
year = {Mon Jan 04 00:00:00 EST 2021},
month = {Mon Jan 04 00:00:00 EST 2021}
}
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