| Photothermal therapy is a new type of cancer treatment,which has attracted wide attention due to its advantages of non-invasiveness and low side effects.Photothermal therapy can ablate tumor cells via local hyperthermia gengrated by photothermal agents under irradiation.Therefore,the performance of photothermal agents is particularly important for photothermal therapy.Boron dipyrromethene(BODIPY)is a kind of dye with high molar extinction coefficient,good photostability and easy modification,which is widely used in the research of cancer treatment.The absorption and emission wavelengths as well as the photothermal conversion properties of molecules can be adjusted through reasonable design of molecular structures.The construction of organic polymer nanomaterials can improve the stability and blood circulation time of drugs in vivo while solving the problem of drug hydrophobicity,which is beneficial to their aggregation in tumors.Currently,physical encapsulation and chemical bonding are the main methods for preparing organic polymer nanomaterials.Based on this,BODIPY molecules were selected as our research objects to construct photothermal agents with higher performances through the design of molecular structures and the introduction of amphiphilic polymers,and combined with other therapies to further improve the therapeutic effect of BODIPY in tumor treatment.The specific research contents are as follows:(1)To explore the influence of conjugated structures on the properties of organic molecules,three BODIPY molecules with different conjugated structures were synthesized.It is found that these BODIPY molecules exhibit the red-shifted absorption and emission wavelengths,enhanced intersystem crossing and weakened radiative transition with the increase of their conjugated structure.After assembly into nanoparticles,the radiative transition and the intersystem crossing of BODIPY molecules are quenched due to the aggregation effect,which further promotes the nonradiative transition process to generate heat.Therefore,the organic polymer nanomaterials obtained by co-assembly of BODIPY with the largest conjugated structure and the block copolymer F 127 are excellent in tumor therapy in vivo.(2)In order to explore the influence of molecular structures on the performance of organic molecules,benzene,naphthalene,anthracene and pyrene groups were introduced respectively at the meso position of BODIPYs.The experiment results show that the absorption and emission spectra of BODIPYs with different groups as well as the photothermal properties of the organic polymer nanomaterials from co-assembly with the block copolymer F127 show little difference.But the spin-orbit charge transfer-intersystem crossing induced by anthracene group promotes the generation of singlet oxygen under the same conditions.In in vitro experiments,the combination of photothermal and photodynamic therapy exhibits better performance.(3)To enhance the antitumor effect,a BODIPY molecule with both copper chelation function and photothermal effect were synthesized.And the organic polymer nanomaterials co-assembly with BODIPY and MPEG2000-DSPE could chelate copper ions and lead to fluorescence quenching.Under laser irradiation,the nanomaterials showed good photothermal effect.In in vivo antitumor experiments,the combination of the two therapies exhibits enhanced antitumor effects compared to copper chelation or photothermal therapy alone.(4)To improve the loading efficiency of polymer physical encapsulation,the hydrophilic PEG were conjugated with near-infrared BODIPY,and polymer-based BODIPY molecule was obtained,which could self-assemble into organic polymer nanomaterials.By introducing heavy atoms,the combination of photothermal and photodynamic therapy was realized,which significantly improved the antitumor properties of the nanomaterials.In addition,the nanoparticles can perform photoacoustic imaging and near-infrared fluorescence imaging of tumors,realizing the integration of diagnosis and treatment of phototherapeutic materials. |
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