Design And Synthesis Of Organic Bioinformatics Materials For Phototherapy And Sensing Applications

Organic bioinformatics materials have been studied and applied in bioinformatics molecular detection,especially in cancer therapy.Photothermal therapy and photodynamic therapy based on related materials have excellent spatial resolution and non-invasiveness,and less damage to healthy tissue.Compared with traditional chemotherapy and radiotherapy,phototherapy shows good application prospects.Inorganic nanoparticles with photothermal and photodynamic functions are difficult to apply because of their difficult metabolic properties and unknown long-term biological toxicity.Therefore,the preparation of low toxicity,high Biofouling Resistance and metabolizable materials has important research significance and application prospects.Organic conjugated semiconductor materials have been extensively studied due to their abundant structure,easy adjustment and modification.In biological applications,water-soluble organic conjugated materials are favored by researchers because of their good dispersion and low toxicity.Based on the biosafety of materials,a novel organic nano-therapeutic agent with high stability and good biocompatibility was prepared by using polyethylene glycol,amphoteric ions and small molecular micelles.It has the ability of clearing human body through urine excretion to meet the specific needs of diagnosis and treatment.The research contents of this paper include the following four parts:1.We describe the synthesis of a PEGylated NIR dye（DPP-PEG）with high aqueous solubility for in vivo PA imaging and fluorescence imaging.DPP-PEG exhibited perfect EPR effect as well as renal excretion due to its molecular mass of 11 k Da,well within the size limit of 40 k Da for renal excretion.Long retention time in tumor makes DPP-PEG very suitable for photothermal therapy.DPP-PEG showed excellent photothermal therapy under NIRF imaging,photothermal imaging and photoacoustic imaging.2.Dual-modal imaging and dual-modal therapy provides multiple complementary theranositic features.The theranositic agent has favorable renal excretion and low cytotoxicity,making it of great interests in the nanomedical field.Herein,a water-soluble conjugated zwitterionic polymer（DPP-SPMA）with low-fouling and low cytotoxicity was prepared and used for fluorescent/PA imaging guided PTT/PDT therapy.The in vivo imaging results showed that the DPP-SPMA had excellent enhanced permeability and retention effects.The fluorescent imaging demonstrated that the DPP-SPMA was excreted by renal metabolism because the controlled molecular mass was less than the renal filtration threshold.The DPP-SPMA shows a photothermal effect under 730 nm irradiation and an excellent singlet oxygen generation capacity for the PDT therapy under 635 nm irradiation.The high accumulation of DPP-SPMA by passive targeting around the tumor stimulated excellent synergistic photodynamic therapy and photothermal therapy.As a result,the water-soluble zwitterion DPP-SPMA was well suited for fluorescent/PA dual-modal imaging and significant antitumor activity in vivo via synergistic photodynamic therapy and photothermal therapy.3.Surfactants with fluorescence groups find their applications in sensor and assemble processes study for their sensitivity and convenience.Herein,we successfully synthesized a serial of quaternary ammonium Gemini surfactants（m-TBT-m）with conjugated thiophene-benzene-thiophene spacer.Emission properties study showed fluorescent Gemini surfactants assembled into micelles and hydrophobic chain length has significant effect on the critical micelle concentration（CMC）.The CMC of 8-TBT-8、10-TBT-10、12-TBT-12、14-TBT-14and 16-TBT-16 are 1×10^-6mol/L、4×10^-6mol/L、1×10^-5mol/L、2×10^-5mol/L and 4×10^-5mol/L respectively.It is obviously that the CMC of these fluorescent Gemini surfactants increases with the increase of hydrophobic chain length.Due to the generation of signlet oxygen by quaternary ammonium group,the micelle of 8-TBT-8 showed excellent photodynamic therapy performance and PDT was realized under white light.4.A ligand-free fluorene-alt-phenylene copolymer has been newly synthesized as a fluorescent chemosensor for a copper（Ⅱ）ion（Cu（Ⅱ））.The fluorescence of the copolymer can be efficiently and specifically quenched by the addition of Cu（Ⅱ）in nucleophilic solvents such as DMF and DMSO,while no significant fluorescence quenching in low nucleophilic solvents such as 1,4-dioxane and THF was observed.UV–vis spectroscopic measurements for the mixture of the conjugated polymer and Cu（Ⅱ）revealed the presence of a reduced Cu（I）ion in the solution.A fluorescence recovery phenomenon of the polymer was observed at low temperature,which suggests that the quenching and reducing mechanism is most probably due to a photo-induced electron transfer from the polymer to Cu（Ⅱ）.Such the fluorescent chemosensor proposes a novel strategy for highly selective conjugated polymer-based chemosensors for various target analytes,albeit ligand-free.In conclusion,we have designed and synthesized a series of photothermal and photodynamic therapeutic materials with low toxicity and strong metabolic ability,including nonionic polyethylene glycol,near infrared materials of amphoteric ions and cationic micelles.At the same time,we studied the mechanism of a ligand-free polyfluorene-benzene material for the detection of copper ions in nucleophilic reagents.This paper has made some explorations in the field of metabolic bioinformatics materials,which will provide a basis for further exploring the application of bioinformatics materials in the field of biomedicine.