1. Surface Functionalization of Hepatitis E Virus Nanoparticles Using Chemical Conjugation Methods
- Author
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Marie Stark, Mo Baikoghli, Chun Chieh Chen, and R. Holland Cheng
- Subjects
0301 basic medicine ,Insecta ,chemical conjugation ,General Chemical Engineering ,Nanoparticle ,Bioengineering ,targeting ligand ,Conjugated system ,virus-like particles ,General Biochemistry, Genetics and Molecular Biology ,Hepatitis ,law.invention ,03 medical and health sciences ,Issue 135 ,law ,Hepatitis E virus ,Animals ,Humans ,Nanotechnology ,Psychology ,Cancer ,Cysteine replacement ,General Immunology and Microbiology ,Chemistry ,Liver Disease ,General Neuroscience ,Ligand (biochemistry) ,Small molecule ,Combinatorial chemistry ,multivalent ligand display ,Good Health and Well Being ,030104 developmental biology ,Recombinant DNA ,Nanoparticles ,Surface modification ,hepatitis E ,Cognitive Sciences ,Biochemistry and Cell Biology ,Nanocarriers ,Digestive Diseases ,Biotechnology ,Cysteine - Abstract
Virus-like particles (VLPs) have been used as nanocarriers to display foreign epitopes and/or deliver small molecules in the detection and treatment of various diseases. This application relies on genetic modification, self-assembly, and cysteine conjugation to fulfill the tumor-targeting application of recombinant VLPs. Compared with genetic modification alone, chemical conjugation of foreign peptides to VLPs offers a significant advantage because it allows a variety of entities, such as synthetic peptides or oligosaccharides, to be conjugated to the surface of VLPs in a modulated and flexible manner without alteration of the VLP assembly. Here, we demonstrate how to use the hepatitis E virus nanoparticle (HEVNP), a modularized theranostic capsule, as a multifunctional delivery carrier. Functions of HEVNPs include tissue-targeting, imaging, and therapeutic delivery. Based on the well-established structural research of HEVNP, the structurally independent and surface-exposed residues were selected for cysteine replacement as conjugation sites for maleimide-linked chemical groups via thiol-selective linkages. One particular cysteine-modified HEVNP (a Cys replacement of the asparagine at 573 aa (HEVNP-573C)) was conjugated to a breast cancer cell-specific ligand, LXY30 and labeled with near-infrared (NIR) fluorescence dye (Cy5.5), rendering the tumor-targeted HEVNPs as effective diagnostic capsules (LXY30-HEVNP-Cy5.5). Similar engineering strategies can be employed with other macromolecular complexes with well-known atomic structures to explore potential applications in theranostic delivery.
- Published
- 2018
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