Construction Of Stimuli-responsive Nanocarriers Using Supramolecular Host/Guest Recognition Based On Cyclodextrin And Ferrocene

In recent years,polymeric nanoparticles derived from the self-assembly of amphiphilic block copolymers have show great potential as drug delivery systems owning to the ability of improving the solubility of hydrophobic anticancer drugs as well as prolonging the circulation time by the hydrophilic shell.Compared to the complicated synthesis of traditional amphiphilic block copolymers,the preparation of supramolecular amphiphilic block copolymers by using the host/guest pair as the block junctions greatly simplifies the difficult of synthesis.However,no matter traditional or supramolecular amphiphilic block copolymers,the premature release of loaded drug greatly increase off-target exposure and reduces drug concentration in cancer cells due to the in vivo instability resulted from the disassembly of polymeric nanoparticles during systemic circulation by the high dilution.Now,using cross-linked nanoparticles or unimolecular formulations based on polymers with advanced topology have been developed as two primary strategies to improve the stability of polymeric nanoparticles.Among polymers with advanced topology such as cyclic and star-shaped structure,cyclic polymers have received considerable attention due to their endless chain topology-associated unique properties.However,the current two leading synthesis approaches,i.e.,ring-expansion polymerization and ring-closure reaction have provided only limited accessibility to cyclic polymers due to their respectively inherent limitations.Therefore there is considerable scope for the development of novel and efficient strategies toward cyclic polymers to significantly simplify the available synthetic methods.What's more,cross-linking often suffers from additional complicated chemistry design.To overcome the issue,we developed an extremely straightforward and robust cross-linked strategy and a novel and efficient strategies toward synthesis of cyclic polymers to improve the stability of polymeric nanoparticles by using supramolecular host/guest recognition based on cyclodextrin and ferrocene.The detailed contents were listed as follows:1.In the second chapter,we developed the multifunctional CD unit and realized an one-pot preparation of dual-redox sensitive and stabilized supramolecular nanocontainers by self-crosslinking of a multifunctional ?-CD unit that combines a host cavity for an oxidation-mediated reversible complexation with the ferrocence(Fc)guest molecule with lipoic acids(LAs)-decorated primary and secondary faces for reversible in-situ crosslinking by the reducible disulfide links.The DOX-loaded cross-linked polymer(DOX@CL P)exhibited more stabilized and dual-redox responsive drug release behaviors.Moreover,the DOX@CL P displayed enhanced antitumor efficacy in a BEL-7402 tumor-bearing mice model and reduced side effects toward normal organs in vivo.In summary,we have developed the multifunctional CD unit and realized an one-pot preparation of dual-redox sensitive and stabilized supramolecular nanocontainers for anticancer drug delivery,and the supramolecular nanocontainers may have potential clinical utility.2.In the third chapter,by using both star-shaped polymers(3-PCL–Fc)and ?-cyclodextrin(?-CD)as the dual templates,we controlled synthesis of ring-like colloids and cyclic polymers via a dual-template approach in this study.The star-shaped polymers as the first template generated a ring-like structure,and dimension of the ring was deteminned by the molecular weight(MW)of the star template and the cross-linking degrees.We transformed the ring-like structure into a cyclic polymer by using ?-CD as the second template restricting the ring thickness to a value of a ?-CD's height.And the successful synthesis of ring-like colloids and cyclic polymers was confirmed by direct atom force microscopy(AFM)and transmission electron microscopy(TEM)observations.The resulting cyclic polymers showed reduction-triggered destruction of the cyclic topology toward promoted release of the encapsulated cargoes due to the existence of crosslinked disulfide bridges in the structures.The reported “dual-template” approach is not only a valuable complementary to the current synthetic strategies toward ring-like colloids and cyclic polymers,but also construct a connection that bridges ring-like colloids and cyclic polymers.