Construction And Characterization Of Novel Near Infrared Aza-BODIPY Theragnostic Agents

Phototheranostics has received widespread attention from researchers due to its advantages such as non-invasive and real-time treatment.In recent years,based on the in-depth research of phototheranostics,most organic therapeutic agents still face challenges such as limited tissue penetration depth,photobleaching,and single function.Therefore,the construction of efficient and multifunctional therapeutic agents has become the focus of research in many fields such as material science and biomedicine.Based on the fact that Aza-BODIPY has excellent optical properties,good stability,and functionalization of its structure,we developed a series of novel near infrared（NIR）absorbing Aza-BODIPY therapeutic agents and conducted an in-depth investigation of their performance,and corresponding theoretical calculations in combination to reveal the“structure-property”relationship,and investigated the potential applications of Aza-BODIPY therapeutic agents in tumor treatment.The research contents of this thesis are as follows:1.Thiophene and N,N-dimethylaniline were introduced into the Aza-BODIPY backbone as electron donors with the parent nucleus to form electron donor-electron acceptor（D-A）structure,namely BDP-4.BDP-6 was obtained by the formylation reaction of BDP-4.Based on the photophysical/chemical properties and excited state dynamics,and combined with theoretical calculations,we found that both BDP-4 and BDP-6 have NIR absorption and fluorescence emission properties,but the ability of BDP-4 to undergo radiative transition is more significant,while BDP-6 can undergo effective intramolecular photoinduced electron transfer（IPET）and intersystem crossing（ISC）processes,thus providing strong support for the excellent singlet oxygen（¹O₂）generation（Φ_△=0.265%）and photothermal properties（η=50.13%）of BDP-6.BDP-6 was further encapsulated in Pluronic^?F-127 to form nano micelles（BDP-6@F127 NPs）with good water solubility.Excitingly,the BDP-6@F127 NPs retained photodynamic therapy/photothermal therapy（PDT/PTT）properties of BDP-6 well with excellent stability.As shown by the results of cytotoxicity experiments,BDP-6@F127 NPs possess the advantages of PDT/PTT in combination for tumor treatment,which is a new strategy for efficient tumor treatment.2.Based on the molecular engineering theory,different substituents（thiophene,α-bromothiophene and benzothiophene）were introduced at the 1-,7-positions in the Aza-BODIPY backbone to obtain three NIR organic small molecule dyes denoted as BDP-4,Br-BDP-4,and ph-BDP-4,respectively.By comparing the optical properties of these compounds,we found that the spectra of Br-BDP-4 and ph-BDP-4 were significantly red-shifted compared to BDP-4,indicating that the substituent effect can modulate the spectra by adjusting the structure of the molecule.BDP-4 was used as a control compound,Br-BDP-4and ph-BDP-4 as well as their nanoparticles formed by the encapsulation of both with bovine serum albumin（BSA）were further investigated for photothermal and photodynamic properties,respectively.The ¹O₂ generation ability of Aza-BODIPY was low,and the reason for the low ¹O₂ quantum yields of these compounds was further explained by theoretical calculations.The results obtained from photothermal and photoacoustic imaging experiments indicated that the nanoparticles retained photothermal therapy/photoacoustic imaging（PTT/PAI）properties of original single molecules well,and especially Br-BDP-4 has a great potential to be a new class of photoacoustic imaging contrast agent for photothermal therapy in tumor treatment.