Application Of Nanotechnology In Cell Functionalization And Theranostics

DNA is the carrier of genetic information,and DNA nanotechnology separates this molecule from its biological background and uses it as a versatile tool for nanostructural engineering and material assembly.Thanks to the inherent biocompatibility,self-assembly ability and structural programmability of DNA,DNA nanostructures have made great progress in biomedical engineering such as cell functionalization and theranostics.DNA has many advantages over other materials in cell functionalization.First,DNA is cheap,highly pure,and can be further modified anywhere in the DNA sequence.Secondly,the interaction between DNA molecules mainly follows the Watson Crick base pairing rules,so we can predict the form of DNA assembly on the cell.At present,there are many kinds of DNA used for cell functionalization,such as single stranded DNA,framework nucleic acid,aptamer and so on.DNA nanostructure is an ideal carrier of nanomedicine in disease diagnosis and treatment.DNA does not produce harmful byproducts;DNA nanostructures can accumulate in solid tumors and have specific organ-targeting properties.In this paper,we designed a responsive DNA nanostructure to establish artificial cell communications and build a promising clinical nanometer theranostics carrier through the rational design and modification of DNA nanostructure.The research contents are as follows:(1)Programming cell communications with pH-responsive DNA nanodevicesIt is very important in cell biology and even clinical medicine to artificially construct communication between cells in response to changes in cell microenvironment during cell growth and differentiation.Based on this,we developed a pH-responsive DNA nanoswitch to give cells the ability to establish responsive cellular communication.Through hydrophobic interactions and complementary base pairing,three strands of DNA are modified to the cell membrane and are able to accurately recognize pH changes that alter the DNA conformation,releasing sticky ends that set up cell assembly.We further demonstrate that responsive cell assembly induces cell-cell contact-dependent signal transduction.(2)Treating acute kidney injury with black phosphorus nanosheetsDNA nanomedicine has demonstrated that two-dimensional sheets of DNA framework can be targeted to the kidney.As a new two-dimensional material,black phosphorus nanosheets have the properties of two-dimensional sheet structure and electronegativity of the material,which guarantee their targeting to the kidney and provide potential for the treatment of kidney diseases.We have constructed a novel drug delivery platform based on black phosphorus nanosheets to remove excess reactive oxygen species for renal therapy.We verified the broad-spectrum scavenging ability of reactive oxygen species and the in vivo targeting ability of black phosphorus nanosheets.Black phosphorus nanosheets can effectively reduce the level of reactive oxygen species in the kidney to treat acute kidney injury.These exciting properties make black phosphorus a promising drug candidate for inhibiting oxidative stress in reactive oxygen species related diseases and provide new insights into the nanomedical treatment of kidney disease.(3)Liposome encapsulated by sequence-specific DNA escapes from the reticuloendothelial systemMost of the nanomaterials are enriched in the reticuloendothelial system after injection,and only a very small amount of the nanomaterials can be delivered to the target.The liver is the main organ of the reticuloendothelial system,so avoiding the uptake of macrophages in the liver can effectively prolong the circulating time of nanoparticles in vivo,thus increasing the utilization of nanomaterials.In the mouse model,DNA origami structures were preferentially accumulated in the kidney,with little accumulation in the liver.Based on this,we use DNA as an stealth coating for nanomaterials to help them escape from the reticuloendothelial system.We found that poly-A DNA-coated liposomes can effectively escape macrophage uptake and help to reduce liposome accumulation in normal liver.