Study On Fluorination And Ligand Configuration Changes Enhance The Photothermal And Antitumor Properties Of Conjugated Polymers

With the increasing incidence of cancer,cancer treatment has become one of the medical hotspots in the international community.Although there are currently treatments such as surgery and chemotherapy at the clinical level,but these treatments have certain flaws,So scientists are constantly seeking to explore new cancer treatments.Photothermal therapy is a new type of tumor treatment and has received extensive attention in recent years.Many researchers have done a lot of exploration work on photothermal therapy.Compared with traditional clinical cancer treatment methods,photothermal therapy shows many excellent advantages,such as good biological safety,low toxicity to tissues or cells,local controllability and low cost.There are many types of materials used in photothermal therapy,which can be summarized as organic materials and inorganic materials.Organic photothermal materials are often used as materials for photothermal treatment because of easy preparation,low side effects on tissues,and their ability to modify the structure.Among many organic materials,pyrrolopyrrole diketone(DPP)exhibits excellent light stability and satisfactory molar absorption coefficient,and is widely used in the preparation of optoelectronic materials.It has also been reported in recent years in photothermal treatment.DPP is easy to modify.Modification of different groups to make DPP functional can effectively change its physical and chemical properties.For example,the introduction of chalcogen elements in the conjugated structure can significantly reduce the overall energy gap and increase the conjugate effect.In addition to chalcogen elements,electron-withdrawing groups are also commonly used groups for compound modification.In recent years,people have paid great attention to polymers substituted with electron-withdrawing groups to improve the photoelectric properties of materials.Among these groups,the fluorine atom is the most popular unit.Because the F atom has an electronegativity of 3.98 eV and a small van der Waals radius of 1.35 A,compared with non-fluoride,fluoride can not only effectively reduce the level of the highest occupied molecular orbital(HOMO),but also can Internal interactions(such as F..S,F..H and F..π)to improve molecular planarity.For these reasons,fluorination in conjugated polymers may provide a new method to achieve high-performance photothermal agents.In addition,fluorine element is also an important element in drug design.The introduction of fluorine element can improve pharmacokinetic properties,change the molecular conformation and increase the affinity for the target protein.And block the site of metabolic instability,thereby improving the metabolic stability of the drug.For this reason,the fluorination of photothernal materials can be used as a key strategy for improving anti-tumor properties.In the first part of the study,compared with the non-fluorinated DPP-SS,the fluorinated DPP-SF showing longer wavelength absorption due to the narrower energy gap.Finally,DPP-SF and the hydrophilic group DSPE-PEG2000 were used to produce water-soluble nanoparticles DPP-SF NPs by co-precipitation,and their photothermal conversion efficiency in vitro was reach up to 52%.Cell Proliferation test showed that under the irradiation of 808 nm near infrared laser,the effective semi-inhibiting concentration for A549 cells was as low as 8.9 μg/mL.Importantly,excellent biocompatibility and high tumor ablation ability have been demonstrated once again on the subcutaneous A549 tumor-bearing mouse model.In addition,DPP-SF NPs has demonstrate great PAI/PTT capabilities.In the second content,using DPP as the electron acceptor,and using different symmetric forms of diselenophene as the electron donor,respectively prepared DPP-BSe,DPP-DSe and DPP-ESe,explore the effect of symmetrical form of ligand on the photothermal conversion ability of conjugated polymers.Among the three electron donors,DPP-BSe with the diselenophene of central symmetry has the best photothermal performance.This is due to central symmetry of diselenophene helps to enhance the planarity of the molecular skeleton,make the dihedral angle reach-179.98°,which is more conducive to charge transfer within the molecule.After being coated with DSPE-PEG2000,nanoparticles with a particle size mainly distributed between 50 to 70 nm.The photothermal conversion efficiency of DPP-BSe NPs is 42%,and exhibit good photothermal therapy effect on tumor cells both in vitro and in vivo,and can inhibit the growth of subcutaneous tumors while ensuring good biocompatibility.In addition,it show good ability of photoacoustic and photothermal imaging,which has a guiding significance for photothermal therapy.In summary,we have successfully achieved the change of photothermal performance of photothermal materials by introducing F atoms into the molecular structure and changing the symmetry of the ligand group configuration.This work is expected to provide new ideas for the design of photothermal materials and promote the development of photothermal therapy.