Albumin Self-assembling Nanoprobe For Accurate Diagnosis And Treatment Of Atherosclerosis Vulnerable Plaque

Acute cardiovascular and cerebrovascular events induced by Atherosclerosis and vulnerable plaque rupture have become the "first killer" threatening human health.At present,clinical diagnostic methods for vulnerable plaque rupture have imaging methods such as intravascular ultrasound and positron emission tomography,and the main treatments are hypolipidemic and anticoagulant drugs and stent surgery.But for AS vulnerable plaques,there are still defects in the diagnosis and treatment.For example,imaging methods have low resolution,and can only determine the morphological size of the plaque,and can not evaluate the stability of the internal structure of the plaque;stents have high cost and are prone to secondary obstruction;and statins and aspirin also exist liver damage,easy bleeding and other side effects,which cannot be fundamentally prevented AS plaque rupture.Therefore,it is urgent to develop an in situ,highly sensitive,high-resolution imaging method and a treatment strategy with good stability,small side effects and high efficacy,and achieve the diagnosis and treatment of AS vulnerable plaque at the molecular level.Studies have shown that the rupture of vulnerable plaque is closely related to inflammatory response,and the imbalance of hydrogen peroxide(H2O2)/glutathione(GSH)caused by oxidative stress is a key factor regulating inflammatory response,so H2O2/GSH is a molecular target to monitor plaque inflammatory response status and anti-inflammatory treatment to provide accurate diagnosis and treatment of vulnerable plaque.However,due to the deep plaque position,the currently developed probes are difficult to achieve in situ monitoring,and the existing antioxidants that regulate redox balance,such as curcumin,also have poor water solubility and low bioavailability.Therefore,it is necessary to further develop a highly targeted,biocompatible material to achieve in situ detection and efficient treatment of vulnerable plaque in vivo.The self-assembled biomimetic nanomaterials based on bovine serum albumin(BSA)have emerged in recent years to provide an opportunity to achieve the above goals.The materials have high water solubility,good biocompatibility,strong coating ability and no interference absorption.They can be used as imaging agents and nanomedicine for deep tissues in situ imaging detection and targeted therapy in living organisms.Therefore,based on the high content of H2O2 caused by redox imbalance in plaque and the unique inflammatory microenvironment of plaque area,the nanoprobe/high-efficiency anti-inflammatory nano drug of redox response can be developed by means of the advantage of BSA to achieve accurate diagnosis and treatment of AS vulnerable plaque in the living body.In view of this,this paper utilizes BSA and near-infrared small-molecule probes/curcumin self-assembly into nanoprobe and nanodrug,which realizes the monitoring of plaque vulnerability in vivo based on redox reaction,and achieves high-efficiency anti-inflammatory and anti-oxidation treatment:1.For the change of H2O2 and GSH content caused by the imbalance of redox state in the plaque,two types of near-infrared probes,specific for glutathione(GSH)/hydrogen peroxide(H2O2)redox couple,were used to introduce the self-assembly of BSA,forming a BSA-Cy-Mito nanoprobe for in vivo photoacoustic imaging of redox status.Such BSA-based self-assemblies on one hand processed good biocompatibility and long blood circulation for high EPR effect and plaque accumulation and on the other hand displayed strong GSH-and H2O2-dependent absorbance at 765 and 680 nm,which enabled simultaneous photoacoustic detection of GSH/H2O2 with high specificity and sensitivity.Using BSA-Cy-Mito as an in vivo GSH/H2O2 indicator,accurate detection of the redox-related inflammatory process was realized both in oxidized low-density lipoprotein(ox-LDL)-activated macrophages and high fat diet-fed apolipoprotein Edeficient(ApoE-/-)mice.Systemic administration of BSA-Cy-Mito further enabled differentiation of vulnerable plaques from stable ones based on their different redox states.Therefore,this sensitive redox-responsive PA nanoprobe may be a powerful tool for early identification of rupture-prone plaques and help in implementing successful preventative therapeutic strategies.2.For AS plaque rupture which effects by oxidative stress and inflammatory response,we used BSA as a drug carrier to synthesize a macrophage membrane-coated albumin-curcumin nanomedicine(MC-BSA-Cur)to improve the therapeutic effect of curcumin on AS.The nanomedicine is mainly composed of three parts:1)macrophage membrane with homologous targeting to macrophages,which enhances the enrichment of the drug at vulnerable plaque;2)Bovine serum albumin which has high drug loading rate and high water solubility;3)Curcumin,a drug with obvious anti-inflammatory and anti-oxidation effects.The study found that our synthesized nanodrugs are highly stable,can effectively reduce the production of foam cells and pro-inflammatory factors,reduce the level of H2O2 in macrophages,and have obvious anti-inflammatory effects.Later studies are expected to be effective in achieving intervention and treatment of vulnerable plaque in vivo.