Construction Of Aptamer-Based Nanomaterials And Their Applications In Microbiological Analysis And Protein Delivery

The development of nanomaterials has received great attention since the 20 th century and Richard Feynman first explored the possibility of maneuvering materials at the atomic or molecular level.Due to the unique structural and physicochemical properties,nanomaterials have promoted the interdisciplinary development between many disciplines including materials,physics,chemistry,medicine and so on.Nanomedicine is one of the most important research topics and nanomaterials have played an important role in disease analysis,drug delivery,and cancer therapy.In the related fields of medical diagnostics and drug delivery,nanomaterials generally need to be in direct contact with various living substances such as nucleic acids,proteins,cells and tissues,which requires nanomaterials with better biocompatibility and selectivity.The development of interdisciplinary subjects has encouraged human beings to understand the world within living cells.Choose nanomaterials with favorable biocompatibility according to the molecular mechanisms of cells is a new perspective in nanomedicine.For example,some inorganic nanomaterials can be intracellular synthesis based on the metabolic pathways of living cells and nanomaterials obtained from organisms own inherent advantages in subsequent in vivo applications.As the major carrier of genetic information,nucleic acid is an important biological macromolecule.In the early 1990 s,some nucleic acid sequences were found to bind with certain substances with high specificity and such sequences were called aptamers.Aptamers have a wide range of targets including metal ions,small molecules,proteins,cells,etc.Owing to the high selectivity and strong binding affinity,aptamers have been evaluated as “chemist’s antibodies”.In recent years,aptamers have played an important role in improving the selectivity of nanomaterials and are widely used in medical diagnosis,bioimaging and drug delivery.In this work,we rationally designed several aptamers-based nanomaterials through combining the recognition functions of aptamer and unique properties of inorganic/biological nanomaterials.We further explored the applications of these nanomaterials in target separation,bacterial detection and drug delivery.(1)We have synthesized Fe3O4@m Ti O2 magnetic core-shell nanomaterial through the kinetic control method and further functionalized with aptamers on the surface.This magnetic nanoprobe exhibited excellent performance in microbial separation and photocatalytic sterilization.This work provides new ideas for the design of microbiological scavenger and detection probe.(2)We have constructed an aptamer-guided magnetic capture probe and further explored the application in pathogen identification in bacterial bloodstream infection.This magnetic capture probe exhibited excellent selectivity and rapid separation ability for bacteria in blood with different concentrations.Moreover,different targets in blood can be concentrated just by changing the types of aptamers,indicating the universal applicability of this magnetic probe in clinical diagnosis.This work may pave a way for the rapid diagnosis of infectious disease and the design of portable diagnostic devices.(3)We have developed a cell-derived microvesicle-based delivery vehicle and explored their application in drug delivery.Aptamer was introduced to the surface of microvesicle through two methods,including chemical coupling and lipid chimerism.This drug delivery system exhibited excellent biocompatibility and the aptamer significantly improved the selectivity of microvesicles.This work has important clinical significance for the development and design of new drug delivery vehicles.(4)We have explored the way for loading protein into the interior of cell-derived microvesicles and further delivery protein to the cells by microvesicles-based vehicles.Two loading methods named electroporation and membrane fusion were used in this work for protein loading.This work opens up new perspectives for microvesicle loading and also provides insight into the construction of nanoreactors and artificial cells.