Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells
| Autor: | Zijian Zhang, James C. Gumbart, Alexandra Atalis, Emily J. Devereaux, Randall Toy, Pallab Pradhan, Shohini Ghosh-Choudhary, Simran Dhal, Casey E. Vantucci, Nick J. Willett, Jinhwan Kim, Krishnendu Roy, Katie M. Kuo, Jiaying Liu, Jianguo Wen, Da Huo, Kelsey P. Kubelick, Stanislav Emelianov, Zhiheng Lyu, Younan Xia |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
T cell medicine.medical_treatment Bioengineering Janus particles 02 engineering and technology Multifunctional Nanoparticles Monoclonal antibody Article Natural killer cell Mice Immune system medicine Animals Humans General Materials Science Chemistry Mechanical Engineering Myeloid-Derived Suppressor Cells Antibodies Monoclonal General Chemistry Immunotherapy 021001 nanoscience & nanotechnology Condensed Matter Physics Cell biology Rats Killer Cells Natural medicine.anatomical_structure Myeloid-derived Suppressor Cell Nanoparticles 0210 nano-technology Ex vivo |
| Zdroj: | Nano Lett |
| ISSN: | 1530-6992 |
| Popis: | Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune-disorders. 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, multi-step, 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. 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. |
| Databáze: | OpenAIRE |
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