Pillar[5]arene-based Supramolecular Drug Nanocarrier And Light-harvesting System: Construction And Application

In recent years,with the development of supramolecular chemistry,supramolecular self-assembly based on the noncovalent interaction plays more and more important role in chemistry,biology,and materials.Pillar[n]arenes,as a new supramolecular macrocycle,have been gradually used in the field of drug delivery systems,light-harvesting,and smart window due to their brilliant ability of host-guest interaction and structure.In this dissertation,based on the supramolecular self-assembly of water-soluble pillar[5]arenes and guest molecules,we have constructed novel supramolecular functional materials and investigated their potential application in drug delivery and light-harvesting systems,which contains the following five parts:In the first part,dual acid-responsive bola-type supramolecular vesicles have been successfully constructed for efficient intracellular anticancer drug delivery,which is fabricated by the complexation between a water-soluble pillar[5]arene(WP5)and an acid-sensitive guest molecule(G)contanining the 2,4,8,10-tetraoxaspiro[5.5]endecane moiety.Compared with the control system that only has single p H-responsiveness of WP5,the obtained dual acid-responsive supramolecular vesicles exhibit much faster drug release efficiency under the acid microenvironment of cancer cells.Moreover,cytotoxicity experiments confirm that the doxorubicin(DOX)-loaded supramolecular vesicles can not only obviously enhance the anticancer efficiency of free DOX for tumor cells,but also remarkably reduce the side effects on normal cells,suggesting their potential applications in cancer therapy.In the second part,supramolecular prodrug vesicles with efficient property for dual chemotherapy have been successfully constructed from a water-soluble pillar[5]arene(WP5)and a betulinic acid derivative(BA-D)for cancer treatments.Under the acidic microenvironment of cancer cells,both the encapsulated anticancer drug doxorubicin(DOX)and prodrug BA-D can be effectively released from DOX-loaded WP5éBA-D prodrug vesicles for combinational chemotherapy.Furthermore,in vitro and in vivo studies reveal that DOX-loaded prodrug vesicles can obviously enhance the anti-cancer efficiency based on cooperative effect between DOX and BA-D,while remarkably reduce the systematic toxicity in murine tumor model,suggesting great potential applications in combinational chemotherapy for cancer treatments.In the third part,bifunctional supramolecular prodrug vesicles have been successfully constructed based on the complexation between a glutathione(GSH)-responsive prodrug guest molecule(DNS-CPT)and a water-soluble pillar[5]arene(WP5)for cancer diagnosis and therapy.Under the microenvironment of cancer cells with high GSH concentration,7-ethyl-10-hydroxycamptothecin(SN-38)with strong yellow fluorescence can be efficiently released from the prodrug DNS-CPT for drug location and cancer therapy.In the fourth part,a highly efficient artificial light-harvesting system(ALHS)in aqueous phase with two-step sequential energy transfer process has been successfully constructed based on the host–guest interaction between a water-soluble pillar[5]arene(WP5)and a bola-type bis(4-phenyl)acrylonitrile derivative(BPT),as well as two different hydrophobic fluorescnet dyes(4,7-bis(thien-2-yl)-2,1,3-benzothiadiazole(DBT)and Nile Red(Ni R)).The fabricated ALHS shows an ultrahigh antenna effect(47.8 for the first step and 20.1 for the second step)with a high donor/acceptor ratio of 350:1.It is noted that the obtained WP5éBPT supramolecular nanoparticles possess enhanced aggregation-induced emission(AIE)effect and can function as an ideal donor to realize the first-step of energy transfer from the WP5éBPT assembly to DBT.Moreover,inspired by the sequential energy transfer in nature,Ni R was carefully selected as the second acceptor to fabricate an efficient two-step sequential light-harvesting system based on WP5éBPT-DBT-Ni R assembly,which exhibits a high FRET efficiency of 60.9% and 89.4% for the two-step sequential energy transfer process,respectively.Notably,the emission color changed from light blue to bright green and then to bright red during this process,thus by tuning the molar ratio of DBT and Ni R,a bright white light emission can be achieved with a high fluorescence quantum yield of 23.5%,which showed a strong ability of white fluorescence emission and promising applications in visible-light photocatalysis.In the fifth part,two highly efficient artificial light-harvesting systems(ALHSs)in aqueous solution have been successfully constructed based on the host-guest interaction between a water-soluble pillar[5]arene(WP5)and a bola-type salicylaldehyde azine derivative(HNPD),as well as two different hydrophobic fluorescent dyes(Eosin Y(ESY)and Nile Red(Ni R)).The fabricated ALHSs show an ultrahigh antenna effect(32.5 for the WP5éHNPD-ESY assembly and 30.1 for the WP5éHNPD-Ni R assembly)with a high donor/acceptor ratio([HNPD]/[ESY] =250:1 and [HNPD]/[Ni R] = 200:1).Notably,the formed WP5éHNPD supramolecular nanoparticles perform an enhanced aggregation-induced emission(AIE)effect and can function as an ideal donor to realize the energy transfer from the WP5éHNPD assembly to ESY and Ni R,respectively.Moreover,inspired by the natural photosynthesis systems,the WP5éHNPD-ESY and WP5éHNPD-Ni R nanoparticles were further utilized to catalyze the dehalogenation ofα-bromoacetophenone in water environment with an excellent yield of 55% and 65%,suggesting that the solar energy was successfully harvested and effectively converted into chemical energy.This work not only provides a novel approach for the construction of two highly efficient light-harvesting systems in aqueous solution,but also successfully utilizes the output energy for the photocatalysis dehalogenation ofα-bromoacetophenone,showing a potential application in mimicking natural photosynthesis system.In summary,we have successfully constructed five kinds of supramolecular functional materials based on the host-guest interaction between water-soluble pillar[5]arene and guest molecules,and further investigated their capability in drug delivery and light-harvesting systems,which will provide some valuable references in the field of supramolecular functional materials based on water-soluble pillar[5]arene.