Protein-Mediated Biomimetic Synthesis Of Multifunctional Nanoprobes For Cancer Theranostics

In recent years,nanotechnology has made a series of progresses in the field of cancer theranostics.Among of which,inorganic nanoparticles as a"masterpiece"has attracted much attention for a long time by virtue of its unique physical and chemical properties and excellent chemical stability.However,a great number of traditional chemical methods are still used during the preparation of inorganic nanoparticles.Although related technology and theory become mature,and a series of inorganic nanoparticles with good quality are obtained.Nevertheless,the complicated synthesis process,harsh reaction conditions,and environment-friendly features may limit their further transformation of medical applications.Therefore,we employed biomimetic synthesis strategy and used protein as the biotemplate to synthesize a series of biocompatible nanoprobes for cancer theranostics.1.Protein-mediated biomimetic synthesis of Gd:CuS nanotheranostic agent for tumor diagnosis and treatment.Gd:CuS@BSA nanoparticles were synthesized at physiological temperature by using bovine serum albumin?BSA?as a template in a simple and green protein biomimetic synthesis strategy.The resulting nanoparticles have ultrasmall size,high photothermal conversion efficiency,excellent photostability,and MR/photoacoustic imaging ability.The subsequent Gd:CuS@BSA-mediated PTT result shows high therapy efficacy as a result of their potent NIR absorption and high photothermal conversion efficiency.In addition,toxicity studies in vitro and in vivo verify that Gd:CuS@BSA NPs qualify as biocompatible agents.A biodistribution study demonstrated that the NPs can undergo hepatic clearance from the body.This study highlights the practicality and versatility of albumin-mediated biomimetic mineralization of a nanotheranostic agent and also suggests that bioinspired Gd:CuS@BSA NPs possess promising imaging guidance and effective tumor ablation properties.2.Protein-mediated biomimetic synthesis of MnO2@BSA MR nanosensor for in vitro GSH detection and GSH activated tumor MR imaging.MnO₂@BSA nanoparticles were synthesized at room temperature in situ by using BSA as a biotemplate.According to the enhanced MR signal of after reaction with GSH,MnO₂@BSA was then used as a MR nanosensor for GSH detection in serum.Compared conventional detection methods,it has s great number of characteristics,such as no background interference,simple detection process,and high sensitivity.At the same time,taking into account the ultrahigh concentration of GSH in tumor than normal tissue,the ultra-small size,and excellent biocompatibility of MnO₂@BSA nanoparticles,it was then used for in vivo GSH activated tumor MR imaging,achieving smart tumor diagnosis.3.Endogenous Glutathione S-transferase?GST?-mediated biomimetic synthesis of bimodal nanoprobe for in vivo tumor targeted MR/CT imaging.As an endogenous protein in human body,GST is screened and found with these effective amino acids.Capitalizing on these amino acids and its sequences,GST as intended not only generates highly crystallized gold nanoparticles?AuNPs?with uniform size,but also provides binding sites for Gd³⁺in situ bionic integration on AuNPs.This synthesis is found bioinspired,environmentally benign,and straightforward.The AuNPs@GST^Gd exhibits highly hydrophilicity,good colloidal stability,decent relaxivity,and admiring biocompatibility.Additionally,AuNPs@GST^Gd can selectively target the tumor,and then be cleared from body via a hepatic-and-renal hybrid pattern without obvious systemic toxicity.In summary,this paper has successfully constructed a series of nanoprobes by using of protein biomimetic synthesis strategy,which further promoted the application and development of nanotechnology in the field of tumor diagnosis and treatment.