Magnetothermal Regulation Of Protein Corona On Iron Oxide Nanoparticle For Improved Pharmacokinetic Behavior

Because of their unique magnetic properties,magnetic nanoparticles have attracted wide attention in the fields of drug delivery,disease diagnosis and magnetic hyperthermia.However,due to the formation of protein corona and a series of obstacles in drug delivery,nanoparticles are rapidly removed during the blood circulation,resulting in poor therapeutic effect.Here,we found that the local heat generated by PEGylated iron oxide nanoparticles?IONPs?under an altering magnetic fields?AMF?was able to change the component of protein corona both in vitro and in vivo.Moreover,the change was more obvious when higher AMF was exposed.Specifically,the AMF exposure leaded to integrally decrease of opsonins such as apolipoprotein B-100(apo-B₁₀₀)and immunoglobulins,while it induced the totally enhancement of anti-oponins such as serum albumin and cluster.To explore the mechanism underlying the protein corona regulation by AMF,apolipoprotein B-100(apo-B₁₀₀)with 94.12%decrease and serum albumin with 2.6-folds increase upon AMF exposure were chosen as model proteins.Both fluorescence quenching and CD spectra results indicated that it was derived from the local heat generated by IONPs under the AMF,which decreased the helix and increased random coil of proteins,resulting in the change in binding between NPs and proteins,where apo-B₁₀₀was more sensitive to the local heat than that of HSA.Finally,the strategy was applied for in vivo regulating the protein corona of IONPs,displaying prolonged blood circulation lifetime and increased the tumor enrichment efficiency by 242.3%.This work will provide a new method for in vivo modulating protein corona on magnetic nanoparticles to realize better bioavailability.