Self-assembly And Biological Application Of Superparamagnetic Iron Oxide Nanoparticles Based On M13 Phage Template

Superparamagnetic iron oxide nanoparticles(SPIONs),which have been widely applied in the fields of biology and medicine due to their special magnetic properties and easy modification around particle surface.At present,it has made great consequents in the domains of immunoassay,drug delivery and oncology.However,only 0.7?1.1%of nanomaterials at the clinical level can reach to the target site.Traditionally,high dose SPIONs are often required to overcome low delivery efficiency,while high doses can cause problems such as high treatment costs,increased toxic and side effects,which greatly hinder the clinical application of SPIONs.In this study,free nanoparticles were assembled into fibrous nanoparticle assemblies,which will enhance the targeting and promote the active transport to increase the retention time of SPIONs in the lesion tissue,thereby improving the delivery efficiency of nanoparticles and enhancing the effective internalization of SPIONs.For the sake of controllable preparation of self-assembly targeting high abundance enrichment superparamagnetic iron oxide nanoparticles assembly,a multi-carboxy shell was coated on the ultra-small size SPIONs through a ligand exchange reaction.Meanwhile,targeting peptides and controlled release functional peptides were constructed on the surface of M13 phage by phage display technology,and then the multi-carboxyl nanoparticles were self-assembled into "corn-like"nanoparticle assemblies by covalent bonding under the guidance of a functionalized M13 phage template.The experimental results show that this novel functionalized targeting-release-M 13 phage-nanoparticle assembly has a stable structure and good dispersibility,as well as superparamagnetic properties.SPIONs in the assembly still keep single particle,particle array as a whole is phage fibrous,and the nanoparticles around M13 phage seemed to form "corn-like" grains.After co-cultured with MDA-MB-231 cells for 1 h,the assemblies were abundantly adsorbed into cells with relatively low toxicity at a concentration of 0?160 ?g/mL.And Fe content on the surface and interior of cells was 3.56 times higher than that of free SPIONs.At the same time,there are some disintegration of the assembly after entering the cell.In summary,this novel functionalized targeting-release-M13-nanoparticle assembly can enhance nanoparticle delivery and is expected to increase the effective internalization of the nanoparticles.