Preparation And Biological Application Of Perylenedimide-based Photothermal Agents

Perylenedimide(PDI)and its derivatives are widely used in biological probes,photothermal reagents and other fields due to their excellent chemical and photothermal stability,good optoelectronic properties and easy modification.Recent studies have shown that when the maximum absorption of perylenedimide is above 650 nm,the energy of the absorbed near-infrared light can be converted into thermal energy for photothermal therapy.In order to improve the photothermal treatment effect of PDI reagents,good biocompatibility and deep near-infrared absorption are two main elements.In this thesis,perylenedimide is used as the parent,and the electron donating group is connected at the bay position to make the absorption red shift to the near-infrared region,and then the water-solubility is increased by modification.A series of new photothermal reagents have been obtained and their biological applications have been studied.The details are as follows:1.A compound PDI-Fc with a strong electron-donating pyrrolidine group linked at the bay position and a ferrocene group at the amide position,and a water-solubleβ-cyclodextrin main molecule β-CD-mPEG2000 modified with polyethylene glycol were synthesized.PDI-Fc and β-CD-mPEG2000 can form a 1:1 amphiphilic inclusion complex PDI-Fc?β-CD-mPEG2000 through host-guest interaction.In aqueous solution,PDI-Fc?β-CD-mPEG2000 self-assembled into nanoparticles with a diameter of about 150 nm.The nanoparticles have good absorption in the near infrared at 714 nm.Under 660 nm laser irradiation,the photothermal conversion efficiency of PDI-Fc?β-CD-mPEG2000 nanoparticles was η=46.6%.In addition,cell experiments showed that PDI-Fc?β-CD-mPEG2000 NPs had good biocompatibility,low toxicity and potent tumor cell destruction ability under 660 nm laser irradiation.2.Taking the PDI compound containing the pyrrolidine group at the near-infrared wavelength of 713 nm as the starting material,reacting with Lawson’s reagent to obtain the carbonyl oxygen compounds PDI-1S,PDI-trans-2S,PDI-cis-2S and PDI-3S.Compared to the parent compound,the absorption spectra of these thio compounds are red-shifted to 778 nm,840 nm,840 nm,and 908 nm,respectively.In aqueous solution,PDI-Sx nanoparticles with a diameter of about 80 nm were prepared by the co-precipitation method of the above photothermal reagents and distearoyl-phosphatidylethanolamine-polyethylene glycol with good stability.Under 808 nm laser irradiation,PDI-2S and PDI-3S have good thermal conversion efficiency and photoacoustic imaging ability,and can be used for intracellular photothermal killing of cancer cells.