Spotlights on Recent JACS Publications

摘要

Virus-like particles (VLPs) are excellent candidates for bio-based nanotherapeutics, owing to their monodispersity, well-defined shapes and sizes, and ability to be tailored for the precise placement of chemical tags to conjugate drugs, polymers, and targeting ligands. But there are numerous challenges to developing a successful biopharmaceutical. Chief among them is ensuring that the drug does not evoke an immune response from the patient. One approach to immune evasion involves tagging bio-based drugs with polymers, such as methoxypoly-(ethylene glycol) (mPEG), which has been found to increase a drug's circulation half-life while decreasing antigenicity. Jonathan Pokorski and his team compare mPEG with two other water-soluble polymers-polyacrylate and polynorbornene- when conjugated to icosahedral VLPs, and find vastly different polymer conformations and antibody-shielding potential (DOI: 10.1021/jacs.6b11643). The researchers create the VLP-polymer conjugates and use small-angle neutron scattering and cryo-electron microscopy to investigate the structure and conformation of the polymers on the surface. Among the three polymers tested, polynorbornene offers the greatest antibody shielding while having the smallest hydrodynamic volume. The results may help lay the groundwork for the future development of next-generation biopharmaceuticals based on VLPs.