Based Cell Membranes Coated Nanoparticles For Disease Therapy

Due to the challenges facing synthetic nanoparticle functionalization strategies,there have recently been considerable efforts dedicated toward bioinspired nanotechnology,where design cues for effective design are taken from nature.Considering the inherently biological nature of nanoparticle interactions in vivo,biomimicry is a rational approach toward effective nanoparticle design,as it leverages naturally occurring strategies that have been refined by the process of evolution.Consider the cell,one of the most fundamental units of biology,which is particularly adept at carrying out defined functions within complex environments.Either independently or as part of a multicellular organism,a cell comes into contact with a wide range of proteins,other cells,and extracellular matrices,but elegantly manages to carry out the specific tasks necessary for its survival.Cell membrane-coated nanoparticles inherently mimic the properties of the source cells from which their membrane is derived,bestowing a wide range of functions such as long circulation and disease-relevant targeting.This paper summarizes the application progress of cell membrane coated nanoparticles in the field of diseases.In view of the current problems in the field of nanomedicine,we make use of the technical advantages of cell membrane coated nanoparticles to carry out the following work:1.Although anti-PD-1 immunotherapy is widely used to treat melanoma,its efficacy still has to be improved.In this work,we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better anti-tumor efficacy.We designed the CMSN-GOx method,in which mesoporous silica nanoparticles(MSN)are loaded with glucose oxidase(GOx)and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy.By functionalizing the MSN's biomimetic surfaces,we can synthesize nanoparticles that can escape the host immune system and homologous target.These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues.Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an anti-tumor immune response.We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1,exhibits a better anti-tumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone.Additionally,we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues,for which investigate the effect with the cancer therapy in vivo.2.Chemotherapy for hepatocellular carcinoma(HCC)had not achieved satisfactory efficacy mainly due to the high chemical resistance of HCC.Furthermore,it had toxic side effects on normal tissues and can scarcely kill cancer stem cells(CSCs),which are closely related to tumor progression and metastasis.In addition,photothermal therapy(PTT)can only ablate tumor tissue and lack the ability to specifically kill CSCs.Here,we synthesized a biomimetic nanoparticle with good biocompatibility that was coated with indocyanine green(ICG)and vitamin C(VC)by platelet membranes.The prepared nanoparticles were then injected into an orthotopic nude mouse model of HCC through the tail vein.Due to the immune-evasiveness and tumor-targeting ability of the platelet membranes,it was enriched in the tumor tissues.Under laser irradiation(808 nm),hyperthermia is generated to kill cancer cells while releasing VC to eliminate CSCs.In vivo and vitro,the combined therapy has significant advantages in killing CSCs and inhibiting tumor growth and metastasis.Additionally,we used multimodality imaging to characterize the effect of combined therapy,which leads us to believe that this simple and safe therapeutic model has certain potential for application in the clinical practice of HCC in the future.3.Over the next decade,non-alcoholic steatohepatitis(NASH)is projected to be the most common indication for liver transplantation.At present,NASH treatment has not achieved satisfactory results,owing largely to the complexity of the NASH pathogenesy and cytokine diversity.In this work,we designed the PNM-G-PV method,in which gelatin nanoparticles(G)are loaded with pioglitazone and vitamin E(G-PV)and then encapsulate the surfaces of platelet-neutrophils hybrid membranes(PNM).Inherited from the natural source cells,the PNM shows immune evading ability due to the surface marker comprising a number of "don't eat me" signals,and has double inflammatory enrichment capabilities due to the specific surface adhesion molecules.By functionalizing the gelatin nanoparticles biomimetic surfaces,PNM-G can enhance the targeting of inflammatory sites and enrichment liver tissue.The high expression of matrix metalloproteinase-9(MMP-9)at NASH site enables gelatin nanoparticles to intelligently respond to degradation,and then release vitamin E and pioglitazone for drug treatment.We performed an in vivo analysis of these nanoparticles and determined that our prepared PNM-G-PV,exhibits a better NASH therapeutic effect than therapies using G-PV or PV alone.Moreover,we used the LC-MS to monitor the level of triacylglycerols(TAG)metabolism in liver tissues,for which investigate the effect with the NASH therapy in vivo.