Design And Application Of Two-Photon Organicsulfur Photosensitizers Containing Aggregation-Induced Emission Units

Photodynamic therapy(PDT)is an emerging disease treatment method.It possesses the advantages of few tissue damage,low drug resistance and high spatiotemporal selectivity.Photosensitizers(PSs)play an important role in PDT.However,the traditional PSs are prone to aggregate to decrease the reactive oxygens(ROSs)generation,therefore affecting the therapeutic effect.In addition,limited by the short wavelength excitation(short-wavelength light is easy to be scattered by the biological tissues),these PSs are mainly used in the treatment of superficial diseases.Aggregation-induced emission(AIE)molecules can efficiently suppress the nonradiative transition but promote the intersystem crossing(ISC)in the aggregated state,therefore possessing great application potential in the photodynamic therapy.In addition,combined with nonlinear optical(NLO)effects such as multiphoton excitation,the therapeutic depth of AIE photosensitizers can be greatly improved.However,the design of PSs possess is single and they are difficult to synthesize.Moreover,the PSs with two-photon excitation property are in urgent demand.Therefore,it is very desirable to develop a facile method for realizing AIE PSs with two-photon excitation,which will broaden and deepen the practical applications of PDT.Herein,we selected AIE-active tetraphenylpyrazine(TPP)for PSs design because it is very easy to synthesize and modify.Meanwhile,combined with sulfur “heavy atom effect” and polymerization effect,an advanced methodology for preparing two-photon AIE PSs was achieved while their PDT application was exhibited simultaneously.Our work is given as following:Firstly,based on the economical and environmentally friendly thiol-yne click reaction,six polymers(P1-P6)as well as their model compounds(M1 and M2)were prepared.The introduction of the sulfur “heavy atom effect” in situ can boost the photosensitization in these compounds.Secondly,there are normally three deactivation paths of fluorescence,internal conversion(IC)and ISC in the excited states of PSs,which coexist and compete with each other after the molecular excitation.Merging the AIE units in sulfur-containing PSs could remarkably suppress the non-radiative transition(as reflected by the reduction in the rate of nonradiative transition)to enhance the ISC process to promote the generation of ROSs in the aggregate state.Thirdly,P3 possessed a high singlet oxygen efficiency of 59%,which was much higher than M1(18%)and M2(18%).The theoretical calculation revealed that the energy levels in the singlet and triplet excited states moved closer and got denser as the polymerization degree was increased.Thus,the ISC paths were increased significantly to enhance the photosensitization.Finally,because of the formed donor-π-acceptor(D-π-A)structure in PSs,they have excellent two-photon excitation properties.Combined with the high singlet oxygen generation efficiency,good biological compatibility and superior two-photon excitation property,P3 nanoparticles exhibited an excellent photodynamic therapy toward in vitro cancer cells by two-photon excitation,therefore possessing huge potential in the treatment of deep-tissue diseases.