Application Of Probucol Nanoparticles Self-assembled With Indole Molecule In Theranostics Of Atherosclerosis

Atherosclerosis(AS)is a major cause of cardiovascular diseases(CVDs).Early diagnosis and appropriate treatment measures of AS can reduce the harm of CVDs.In recent years,AS nano-theronastics has rapidly developed,which aims to use a nano-drug delivery platform to provide diagnostic tools and treatment measures for AS simultaneously,in order to achieve the purpose of effective prevention and treatment of AS.However,nanocarriers and excipients,which are inevitably for theranostics,make tedious steps for synthesis and complex composition,leading to inevitable biological toxicity and immunogenicity.Therefore,we purpose to construct a carrier-free AS theranostic platform through a template self-assembly method in this work.This method uses indole molecules(Indocyanine green(ICG)or IR783)as a template to assemble with hydrophobic drug molecule(Probucol,PB),and obtains multifunctional nanoparticles(IPNPs or IRPNPs).The results were as following:(1)IPNPs and IRPNPs both showed excellent phy-chemical properties,which testified the generality of indole molecular self-assembly strategy for delivery of PB.(2)At the cellular level,the obtained nanomedicine displayed multiple therapeutic effects including eliminating ROS,preventing macrophages foaming,and attenuating inflammatory reaction.(3)In the AS mouse model,IPNPs and IRPNPs more effectively accumulated in lesion area than ICG and IR783 via intravenous injection,and the blood circulation time were extended to 24 h.More interestingly,we discovered the fluorescence imaging ability of IR783 was more excellent than ICG,respectively.There results indicated that IPNPs and IRPNPs enriched in the lesions through the high permeability and retention effect(EPR)in the plaques.(4)In the AS mouse model,the plaque area of the IPNPs group was smaller than that of the control group,and the total cholesterol(TC)and Low density lipoprotein(LDL)of plasma were lower than the control group.Moreover,through long-term intravenous injection of IPNPs and IRPNPs,the body weight of mice did not change significantly,and there was no obvious organic damage to important organs.These results indicated the multi-functional nanomedicine not only showed excellent anti-AS efficacy,but also revealed an excellent safety profile.In addition,IPNPs via intravenous delivery showed an excellent therapeutic effect in mice.In summary,the constructed nano-theranosttic platform possesses excellent anti-AS efficacy,provides new insights for the development of new theranostics of AS,and is a universal and promising way for delivery of lipophilic drugs.