Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells

• DOI: 10.1021/acs.nanolett.0c04833
• Publication Date: 2021-01-04T18:29:25Z
• Authors: Jiaying Liu; Randall Toy; Casey Vantucci; Pallab Pradhan; Zijian Zhang; Katie M. Kuo; Kelsey P. Kubelick; Da Huo; Jianguo Wen; Jinhwan Kim; Zhiheng Lyu; Simran Dhal; Alexandra Atalis; Shohini K. Ghosh-...; Emily J. Devereaux; James C. Gumbart; Younan Xia; Stanislav Y. Emel...; Nick J. Willett; Krishnendu Roy
• Keywords: Killer Cells, Natural; 0301 basic medicine; Mice; 03 medical and health sciences; Myeloid-Derived Suppressor Cells; Animals; Antibodies, Monoclonal; Humans; Nanoparticles; Multifunctional Nanoparticles; Rats; 3. Good health

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, 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. 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.