Mimovirus Vesicles Based Bioorthogonal Reaction For Cancer Diagnosis

Nanoparticles have been widely studied for diagnosis as well as drug delivery due to their unique properties,such as high surface-to-volume ratio,improved pharmacokinetics of drugs and high accumulation property in angiogenesis-related disease lesions such as arthritis and tumors via enhanced permeation and retention(EPR)effect.The ligand-mediated targeting(known as active-targeting)strategy of drugs or nanomaterials has played an important role in improving their tumor-targeting efficiency.The traditional ligands such as aptamer,antibody,glucose,and peptide have been widely used improve tumor-targeting efficiency of nanoparticles.However,this active-targeting strategy has limitations for tumor targeting due to inter/intra heterogeneity of tumors.Therefore,an alternative active-targeting strategy that can overcome the heterogeneity for tumor targeting is needed.Metabolic engineering is a biological technique that takes the glycan biosynthetic pathways to generate unnatural glycans containing various chemical groups onto the cell surface and make tumor more uniform.These chemical groups can be specifically targeted via bioorthogonal reaction in vitro and in vivo.This artificial strategy for tumor modification can overcome the heterogeneity of tumors compared with the traditional one but cancer-selective labeling still remains a great challenge.The small size of extracellular vesicles can offer therapeutic benefits,for instance,offer innate biocompatibility,high physicochemical stability,long distance communication,and the inherent ability to interact with cells through signaling,fusion,and delivery.Certain studies have also demonstrated that extracellular vesicles exhibit cell selective fusion,tissue-specific tropism and provided powerful tools to manually introduce functional groups onto them.The VSVG protein is a low-pH-activated viral fusogen that enables highly effective membrane fusion without adverse effects and the expression of VSVG protein on the extracellular vesicles surface could mediate the delivery of functional cargos to the target cells via membrane fusion strategy.Herein we report the one kind of mimovirus vesicle which has VSVG protein and chemical receptor azide groups on the surface.This kind of mimovirus vesicles can selectively label cancer cells both in vitro/in vivo under low-pH tumor environment and mediate the delivery of azide groups.Furthermore,the artificial labeled azide groups can be specifically targeted using bioorthogonal molecules without any side reactions via bioorthogonal click reaction in vitro and in vivo that can used for the tumor imaging.