Application Of Biomaterials Based On Cell Membrane In Early Diagnosis And Precaution Of Cancer

Cancer is the main cause of death in the world,accompanied with an increasing number of cases and deaths.It not only seriously endangers the physical and mental health of patients,but also brings a heavy medical burden worldwide.Early diagnosis and prevention of cancer is the most effective way to reduce mortality.Circulating tumor cells(CTCs)are shed from early or metastatic tumors which usually associated with cancer metastasis and tumor spread and can be detected in the peripheral blood of patients,showing great significance for early cancer screening and diagnosis.The detection,isolation and analysis of scarce circulating tumor cells(CTCs)with immunomagnetic nanoparticles(IMNs)have shown promising outcomes in noninvasive cancer diagnosis.However,the IMNs adsorb nonspecific proteins once entering into biofluids and the formed protein coronas are able to cover surface targeting ligands which limits the detection efficiency of IMNs.Additionally,the interaction between surface targeting ligands and white blood cells(WBCs)significantly limits the purity of CTCs isolated by IMNs.Furthermore,the interfacial collision of nanoparticles and cells has negative effects on the viability of isolated CTCs.All such limitations synthetically restrict the isolation and analysis of rare CTCs for early diagnosis and precision medicine.To solve these dilemmas,an innovative strategy making use of neutrophil-cell membrane functionalized immunomagnetic nanoparticles(Neu-IMNs)were developed.The Neu-IMNs have following advantages: reducing the adsorption of non-specific proteins,enhancing the interaction with CTCs,reducing the interface with white blood cells,and improving the viability of isolated CTCs.In blood samples,The Neu-IMNs demonstrated higher separation efficiency(from 41.36% to 96.82%)and higher purity(from 40.25% to90.68%)compared with those uncoated with cell membrane.In addition,19 out of 20 blood samples of breast cancer patients have successfully isolated circulating tumor using the NeuIMNs,further confirming the feasibility of utilizing the Neu-IMNs to separate CTCs for downstream cell sequencing.This study provides a new perspective for the precise detection,isolation and analysis of CTCs using engineered immunomagnetic nanoparticles,paving the way for the early noninvasive diagnosis of cancer.Apart from the systematic study on early diagnosis of cancer,the nanovaccines that can be used for cancer prevention were also explored.Currently,although studies on cancer vaccines have made some progress,most of these strategies lack the ability to activate the immune system to fight against cancer due to inadequate immune response rates.Combining with synthetic biology methods,lentivirus gene transfection technology and nanotechnology,a genetically engineered cell membrane nanovaccine was designed which can realize cytotoxic T cell activation and immunosuppression reversal to effectively prevent cancer.This nanovaccine was a cell membrane nanovesicle derived from genetically engineered cancer cells containing a costimulatory molecule CD40 ligand(CD40L)and an immune checkpoint inhibitor programmed death-1(PD-1).The co-stimulatory molecule CD40 L along with tumor antigens naturally expressed on the surface of cancer cell membranes were effctively able to stimulate dendritic cell(DC)mediated cytotoxic T cell activation.Meanwhile,the immune checkpoint inhibitor PD-1 could block the PD-1/programmed death-ligand 1(PD-L1)signaling pathway to induce reversal of immunosuppression,therefore enhancing the immune response of cytotoxic T cells to cancer cells.This nanovaccine formula showed good preventive effect in mouse metastatic tumor model.Such vaccine strategy combined with gene technology and nanotechnology represents an emerging personalized cancer vaccine strategy and provides a new way of thinking for various types of cancer prevention around the world.