ABSTRACT
In recent years ，biomimetic nanodelivery system based on cell membrane coating has developed rapidly and shows better biocompatibility and efficacy than traditional nanodelivery systems in a variety of diseases . Macrophages，as members of the immune system ，are closely related to the occurrence and development of a variety of diseases . Macrophages are derived from monocytes and can be polarized into M 1 and M 2 types after corresponding stimulation ： M1 macrophages involved in the proinflammatory reaction and M 2 macrophages involved in the inflammatory reaction . This paper reviews the application status of biomimetic nanoparticles coated with macrophage membrane in disease targeted therapy in recent years . Biomimetic nanoparticles coated with macrophage membrane has shown its high targeting and low immunogenicity in the treatment of malignant tumors （breast cancer ，colorectal cancer ，melanoma，glioma），Alzheimer’s disease ，liver ischemia -reperfusion injury ，atherosclerosis and so on . However，the research of Biomimetic nanoparticles coated with macrophage membrane currently focuses on anti -tumor research and is still in the laboratory research stage .
ABSTRACT
RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP) and siRNA a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS-PEG-OPSS as a crosslinker to synthesize LMWP-siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.