Supramolecular Polymer Assembly And Drug Loading Performance Driven By Hydrogen Bond

Self-assembly is an indispensable process in the formation of life system,and is the source of the formation of life systems.With the development of polymer chemistry,self-assembly of synthetic polymers has become an effective means to construct new structures.And with the development of supramolecular chemistry,the self-assembly system mediated by supramolecular interactions not only achieved the external regulation of self-assembly,but also enriched the structure and function.Hydrogen bonding is one of the typical supramolecular interactions,its application in self-assembly providing new ideas for directly constructing micron-scale vesicle assemblies.Meanwhile,hydrogen bonds is susceptive to the p H and temperature.Therefore,the construction of hydrogen-bonding synergistic supramolecular polymer nano-drugs opens a new avenue for controlled release of drugs in tumors and high-efficiency tumor therapy.However,at present the field still possesses the following challenges:1)There is still a lack of effective preparation technology,it is necessary to design and construct supramolecular polymer nanomedicine with precise control of components and richer functions,and practical synthetic methodologies;2)the effect on tumor curative therapy by the responsive supramolecular polymer nanomedicine based on the self-assembly strategy is still unclear.It is necessary to further explore the hydrogen bond responsive controllable release drug to systematically improve the bioavailability of the drug,clarified the structure-activity relationship between the supramolecular polymer nanomedicine and tumor treatment,and thus developed supramolecular polymer nanomedicine with a more significant curative effect.To understand and address the problems above,this article has carried out the following researches:（1）The morphology of the micron-sized vesicle driven by hydrogen bonding andπ-πstacking effect:The amphiphilic ABA triblock polymer poly（ethylene glycol ethyl ether acrylate）-Poly（N-（6-acrylamidopyridin-2-yl）butyramide-trifluoroethyl-acrylate）poly（die-thylene glycol ethyl ether acrylate）（POEGEA-b-P（DAPA-co-TFEA）-b-POEGEA）was prepared through RAFT polymerization,and the hydrophilic and hydrophobic segments were POEGEA and P（DAPA-co-TFEA）respectively.THF/H₂O（95/5,v/v）was chose as the solvent for solution self-assembly,and the micron-sized vesicle morphology was successfully constructed through the interactions of hydrophilic interaction,the hydrogen bonding andπ-πstacking between DAP itself.（2）The construction of supramolecular polymer nanomedicine based on multiple hydrogen bonding and its anti-tumor effect:The drug carrier（POEGEA-b-P（DAPA-co-TFEA）-b-POEGEA）co-loaded the chemotherapeutic drug carmofur HCFU and the photothermal agent IR780 to construct a supramolecular polymer nano-drug system.The DAP,a hydrogen bonding group,randomly distributed in the side group of the hydrophobic block P（DAPA-co-TFEA）,which could load HCFU through triple hydrogen bonding interaction.The hydrogen bond between DAP and HCFU could be broken by the weakly acidic tumor microenvironment（p H=6.5）,lysosomal environment（p H=5.5）,or photothermal action,resulted in the supramolecular polymer nano-drugs disassembled and the HCFU controllably released.At the same time,combined with the photothermal therapy of IR780,the inhibition of the tumor cells growth was achieved by chemo-photothermal therapy.