Preparation And Characterization Of Supermolecular Contrast Agent Based On The Host-guest Interaction Of Cyclodextrin

Magnetic resonance imaging（MRI）is one of the important medical imaging diagnostic techniques due to its advantages of high spatial resolution and non-radiation damage.And it has played an important role in the diagnosis of Parkinson′s disease,Alzheimer′s disease and cancer.In order to improve its diagnostic effect,gadolinium-based small-molecule contrast agents are often used to enhance imaging contrast in clinic,such as Magnevist（Gd-DTPA）and Dotarem（Gd-DOTA）.However,these types of small-molecule contrast agents have a low relaxation rate and are rapidly metabolized from the body,which prevent imaging for a long time.On the other hand,macromolecular contrast agents are difficult to metabolize from the body,they may cause unnecessary damage to the body.Thus,the best strategy is:when the contrast agent needs to be performed,it can maintain a large molecular size and stay in the body;when the imaging process is finished,it can reduce its molecular size quickly and metabolize rapidly from the body.As the second-genaration host molecule,β-cyclodextrin（β-CD）has been widely used in the structural design of biomaterials due to its good biocompatibility and biodegradability.It can combine with a varity of guest molecules and the competition will occur between different guest molecules.This paper aims to prepare supramolecular polymers containing gadolinium small-molecule ligands by the interaction betweenβ-CD and adamantine（AD）derivatives to improve the relaxation rate of small-molecule contrast agents.And the non-covalent bond connection is beneficial to supramolecular polymers to rapidly metabolize gadolinium out of the body through disassembly.（1）We designed and synthesized the star host polymer（4s PCL-CD）withβ-CD modified at the end group and the linear guest polymer with AD at the end（AD-PLLA-b-P（NIPAM-co-HEMA-DTPA））,then we characterized molecular structures of polymers by ¹H NMR,FT-IR and GPC.In the aqueous solution,the host polymer and the guest polymer were combined withβ-CD and AD to form amphiphilic supramolecular copolymer,which can self-assemble to form spherical polymeric micelles.When polymeric micelles are chelated with Gd³⁺ion,they exhibit T₁ relaxivity as a kind of contrast agent for MRI.When adding AD-NH₂ into polymeric micelles solution,the supramolecular copolymer will be disassembled and its molecular weight will be decreased.In addition,as the drug carrier,the drug loading capacity（DLC）and drug loading efficiency（DLE）of polymeric micelles for DOX were 5.83%and 29.2%,respectively.And due to it dis-asseembly and thermal-response PNIPAM chain,it displays burst release and thermal-response release.（2）We synthesized the amphiphilic block host polymers with side chains containingβ-CD（PCL-b-P（DMAEMA-co-Pg MA-CD））and their molecular structures were characterized by ¹H NMR and FT-IR.And we prepared the small-molecule gadolinium complex（AD-DOTA-Gd）containing adamantyl groups and its structure was verified by ESI-MS.The complexes of host polymer and guest molecule can self-assemble to form micelles in aqueous solution.The morphology and size of micellar particles were characterized by TEM and DLS.The supramolecular contrast agent obtained by freeze-drying polymeric micelles solution.And it has a T₁relaxation rate of 20.7 m M^-1s^-1,which is 2.9 times the T₁relaxation rate of Magnevist(7.1 m M^-1s^-1)under the same conditions.Thus,the supramolecular contrast agent we prepared is a potential gadolinium-based contrast agent.