Fabrication Of Biofunctional Surfaces Based On Host-guest Interaction

Biofunctionalization of material surfaces refers to introduction of specific biomolecules onto surfaces with the aim to promote specific biological functionalities.The surfacefunctionalization has become an important step for the fabrication of biomaterials,such as biosensors,microfluidic channels,tissue engineering materials and implanted materials.The most common method for surface functionalization of biomaterials is based on chemica l covalent bonding.Biomolecules are immobilized onto the material surfaces via covalent chemical bonds between specific sites of biomolecules and different chemical groups on the surfaces,endowing surfaces with different biological functions.However,the covalent functionalization process is often limited because one covalent bonding method might only work for biomolecules with specific reactive groups;the resulted biomaterial surfaces are difficult to be regenerated for recycle use.Alternatively,host-guest interaction based on noncovalent interactions is of increasing interest for surface functionalization due to the advantages such as mild reaction conditions,the ability of self-assembly between molecules,and the response to the external environment and thus this strategy has received extensive attention in the research field of surface functiona lization of biomaterials in recent years.In this thesis,a method based on non-covalent host-guest interaction is developed to realize biofunctionalization of material surfaces.Biofunctional ?-cyclodextrin derivatives with multiple bioactive ligands(?-CD-X7,CD-X(where X refers to the bioactive ligand))are incorporated on the surfaces via the host-guest interaction between ?-cyclodextrin and its guest molecule,adamantane(Ada),endowing the resulted surfaces with specific biological functionality corresponding to the properties of bioactive ligands.The detailed research content is as follows:(1)Construction of bioactive surface for specific binding of protein by the combinat io n of layer-by-layer assembly and host-guest interactionIn this work,we fabricated a supramolecular bioactive surface with specific protein binding capability using two noncovalent interactions as the driving forces.Herein,silico n substrates were alternately deposited with the polyanion adamantane(Ada)-modified poly(acrylic acid)(P(AA-co-Ada))and the polycation poly(allylamine hydrochloride)(PAH)to achieve a multilayered polyelectrolyte film containing “guest” Ada groups.The adamantane groups provided binding sites for biotin-heptasubstituted ?-cyclodextrin(?-CD-(biotin)7,CD-B).The resulted surfaces exhibited high binding capacity of avidin owing to the affinity between biotin and avidin.The experimental results indicated that the surfaces could recognize the target protein avidin while inhibit non-specific protein adsorption.After being placed in a complex physiological solution,the surfaces exhibited the binding capacity and specificity to avidin in the presence of interference proteins.In addition,the avidin/C DB complex could be released by simply treating with sodium dodecyl sulfate(SDS)solution to dissociate the host-guest interaction between CD-B and Ada.After incorporation with fresh CD-B,the “regenerated” surfaces could be repeatedly used for avidin binding and recycled for many times.This strategy of biomaterial surface functionalization is expected to be applicable to the surface modification of biosensors,biochips,and various bioassayrelated materials.(2)Biofunctionalization of magnetic nanoparticles via a versatile supramolec ular approachIn this work,a convenient and versatile approach for biofunctionalization of magnet ic nanoparticles(MNPs)was developed based on supramolecular host-guest interaction.First,magnetic porous Fe3O4 particles stabilized by citrate groups were synthesized via a one-pot hydrothermal method.A thin layer of silica was then subsequently coated on the surface of MNPs using a sol-gel process(MNP@Si O2).Moreover,adamantane(Ada)-terminated silanes were introduced on surface of the MNP@Si O2 particles via a silane coupling method(MNP@Si O2-Ada).Finally,the biofunctional ?-cyclodextrin derivatives(CD-X)were incorporated onto the surface of MNP@Si O2-Ada via the host-guest interaction and three kinds of biofunctional ?-CD derivatives were used in this work.The results of the corresponding bioassays indicated that the functionalized MNPs exhibited unique bioactivity according to the ligands on CD-X.Nanoparticles incorporated with biotinheptasubstituted ?-CD derivatives(?-CD-(biotin)7,CD-B)exhibited high binding ability to avidin specifically and resisted non-specific protein adsorption to avoid interference in a complex biological environment.Nanoparticles incorporated with mannoseheptasubstituted ?-CD derivatives(?-CD-(mannose)7,CD-M)could not only specifica l ly bind to Con A,but also specifically capture Escherichia coli due to the specific affinity to Fim H proteins presented on Gram-negative bacteria.Nanoparticles incorporated with Quaternary ammonium salt-heptasubstituted ?-CD derivatives(?-CD-(QAS)7,CD-Q)exhibited strong biocidal activity against bacteria.This strategy based on the host-guest interaction simplifies the surface modification process of MNPs,which is beneficial to the application of MNPs in biomedicine and biotechnology.In summary,bioactive surfaces were fabricated based on non-covalent host-guest interaction between ?-CD derivatives and adamantane groups.The final bioactivity of surfaces could be modularly designed and easily tailored according to the diverse requirements of applications by incorporating ?-CD derivatives labelled with differe nt ligands.This study offers a new way for surface functionalization of biomaterial and is expected to be applied in bioassay devices and nanomaterials with desired functionality.