Construction Of Galactose-based AIE Photosensitizers And Their Bacterial Agglutination And Photodynamic Antibacterial Properties

Bacterial infection is a serious threat to human life and health.Photodynamic therapy(PDT)has great potential in the treatment of pathogenic bacterial infection due to its advantages such as high spatiotemporal control and low bacterial resistance.Photosensitizers are one of the main factors in PDT,but traditional photosensitizers tend to aggregate in aqueous solution,resulting in the reduced singlet oxygen(1O2)generation.In recent years,aggregation-induced emission(AIE)molecules as photosensitizers have obvious advantages,which show enhanced fluorescence emission and improved 1O2 generation upon aggregation in biological water environment.However,102 has a short lifetime and small effective radii,which often decrease the PDT efficacy.Therefore,weattempt to develop glycosyl-based AIE aggregates as photosensitizer for inducing bacterial aggregation through non-covalent interactions to shorten the distance between photosensitizers and bacteria and thus make full use of 1O2 to achieve efficient PDT killing of bacteria.The main conclusions of three chapters are listed in the following:(1)An AIE-active molecule CTRA with electron donor-acceptor(D-A)structure and carboxyl group was designed and synthesized.The carboxyl group was introduced to provide hydrogen-bond sites for binding with S.aureus as well as the D-A structure accounts for generating 1O2.A β-D-galactose-based amphiphile with a hydrophilic β-D-galactose headgroup and a hydrophobic dodecyl chain,namely DGal,was synthesized to coassemble with CTRA for fabricating AIE aggregates bearing glycosyls.The introduction of galactoses increased the hydrogen bond sites,which further improved the ability of the aggregates to induce bacterial agglutination.Driven by the hydrophobic interaction,CTRA and DGal formed the spherical aggregates bearing galactosyls and carboxyl groups on the surface.By simply changing the molar ratio of CTRA and DGal,the glycosyls distribution on the surface and the molecular arrangement of CTRA within aggregates can be tuned for regulating the ability of aggregates to induce bacterial agglugation and produce 1O2 and thus achieving the regulation of PDT killing efficiency of S.aureus.The results demonstrated that at the CTRA/DGal molar ratio of 1:0.8,the spherical aggregate showed high PDT killing activity of nearly 100%against S.aureus by producing 1O2 to destroy the integrity of the bacterial membrane in bacterial clusters under white light irradiation(20 mW/cm2,30 min).Meanwhile,the fabricated CTRA/DGal showed no obvious cytotoxicity to human normal cells.(2)A cationic AIE-active molecule with D-A structure and galactosyl group,namely TPyGal,was designed and synthesized,which self-assembled into the spherical aggregates bearing galactosyls on the surface for achieving the bacterial agglugation and efficient PDT killing of P.aeruginosa.D-A structure accounts for 1O2 production and galactosyls was introduced to binds specifically to the LecA on the surface of P.aeruginosa.Additionally,cationic pyridine group can bind electrostatically to the negative surface of P.aeruginosa.Driven by multivalent galactose-LecA interactions and the auxiliary electrostatic interaction,TPyGal aggregates can effectively capture and cluster P.aeruginosa.Accompanied with that,TPyGal molecules gradually insert into the bacterial membrane of clustered P.aeruginosa owing to the suitable hydrophobicity,which are further facilitated upon light irradiation.Therefore,under white light irradiation,TPyGal aggregates showed efficient PDT killing against P.aeruginosa.It was demonstrated that under the white irradiation with the intensity of 90 mW/cm2,where 50%of P.aeruginosa was killed within 1 min of irradiation and nearly 100%within 20 min.Combined with the functions of bacterial agglugation,membraneintercalating and 1O2 generation,TPyGal aggregates can effectively promote the healing of mice wound infected with P.aeruginosa under white light irradiation and meanwhile show good biocompatibility.(3)Cationic AIE photosensitizer TPyEt bearing a D-A structure was introduced to coassemble with TPyGal to form the spherical aggregates with galactosyl and cationic groups on the surface for improving the ability of aggregtates to gather P.aeruginosa and membraneintercalating as well as 1O2 production and thus enhancing the PDT killing efficiency.By simply changing the molar ratio of TPyGal and TPyEt,the distribution of galactosyls and cationic groups on the surface and the arrangement of D-A units inside aggregates were tuned for regulating the capability of the agrgegtates to induce bacterial agglugation and membraneintercalating as well as generate 1O2 and further regulated the PDT killing efficiency of P.aeruginosa.The results showed that under the white irradiation of low light intensity(20 mW/cm2,30 min),the PDT activity of TPyGal against P.aeruginosa was only 32.6%.In contrast,89%killing activity against P.aeruginosa was achieved in TPyGal/TPyEt spherical aggregates at the optimal ratio of TPyEt(XTPyEt=0.67).Meanwhile,the fabricated TPyGal/TPyEt spherical aggregates as photosensitizers had no obvious cytotoxicity to human normal cells.