Preparation Of NIR-? Optical Diagnostic Agent Based Conjugated Polymer For Tumor Fluorescence Imaging And Photothermal Treatment

Fluorescence imaging?FI?and photothermal therapy?PTT?in the second near infrared biological window?NIR-?,1000-1700 nm?have become an emerging research hotspot in the fields of molecular imaging,chemical biology and material chemistry.NIR-? FI can realize in vivo imaging with high resolution,high signal-to-noise ratio and deep tissue penetration due to the reduced light scattering and absorption and negligible auto-fluorescence.However,most reported NIR-? fluorescence imaging is achieved under the excitation of an 808 nm laser,which has limited tissue penetration compared with 1064 nm laser.Therefore,NIR-? FI and NIR-? PTT performed with 1064 nm laser can further improve the imaging resolution,signal-to-noise ratio and the therapeutic effect of deep tumor tissue.In this paper,we synthesized square acid polymer-based nanoparticles?PSQPNs?and realized the NIR-? FI-guided NIR-? PTT of cancer with excitation of1064 nm laser.In addition,we further used BDT as the donor to design and synthesize three different conjugated polymers with different receptors and explored the influence of receptors on the absorption and NIR-? fluorescence of conjugated polymers.The specific research of this paper is as follows:1. Preparation of square acid polymer-based nanoparticles and its application in NIR-?a?1300-1400 nm?FI-guided NIR-? PTT with 1064 excitation:square acid polymer?PSQP?was successfully synthesized with phenylebipyrrole?BP?as electron donor and3,4-dihydroxy-3-cyclobutene-1,2-diketone as electron acceptor through copolymerization.PSQP has a strong absorption over 1000 nm and its fluorescence emission can reach about 1300 nm in the NIR-?a region under 1064 nm laser excitation.In order to realize the water solubility of PSQP for biological imaging and PTT,we synthesized an amphiphilic copolymer POEGMA-PPG-POEGMA and prepared nanoparticles PSQPNs by nanoprecipitation method.The mean size of PSQPNs in aqueous solution was about 86±5 nm as measured by TEM.PSQPNs have strong absorption at700-1100 nm with the extinction coefficient of 18.61 L g^-1cm^-1at 1064 nm.The photothermal conversion efficiency of PSQPNs under 1064 nm excitation can reach 38%,which is more than141%higher than that under 808 nm laser irradiation?15.85%?.High NIR-?a fluorescence intensity of PSQPNs can be achieved under 1064 nm laser excitation with maximum emission peak at 1290nm,and the imaging depth of PSQPNs can reach up to 6 mm.Compared with NIR-? fluorescence imaging under 808 nm laser excitation,PSQPNs can improve the signal-to-noise ratio of blood vessels of brain,leg and abdomen by 3 times under 1064 nm laser excitation.Therefore,we applied PSQPNs to tumor mice with colorectal cancer in vitro and in vivo,and found that the fluorescence signal of PSQPNs can reach the maximum enrichment at the tumor site at 12 h.In addition,PSQPNs could be a promising optical diagnostic agent for NIR-?a FI-guided NIR-? PTT.2. Preparation of conjugated polymer nanoparticles with BDT as donor unit and its applications in NIR-? FI and NIR-? PTT:With BDT as the donor,TTQ,DPP and BBT as the acceptors,three different narrow bandgap conjugated polymers,BDT-TTQ,BDT-DPP and BDT-BBT,were synthesized by tin-bromine Stille polymerization.Subsequently,these conjugated polymers were encapsulated into Pluronic?F-127 via a nanoprecipitation method to prepare the conjugated polymer-based water-soluble NIR-? nanoprobes,BDT-TTQ NPs,BDT-DPP NPs and BDT-BBT NPs,respectively.After comparing the photophysical properties and the NIR-? fluorescence imaging effect of these three nanoparticles,we selected BDT-TTQ NPs?absorption at900-1300 nm and fluorescence emission at 1200-1350 nm?as the contrast agent for the NIR-?a fluorescence imaging under 1064 nm laser excitation.Compared with pure water?rising to 33??,the temperature of BDT-TTQ NPs(1 mg ml^-1)in water can rise to 62?under 1064 nm laser irradiation.In addition,BDT-TTQ NPs show excellent thermal stability.All these results provide a possibility of BDT-TTQ NPs for photothermal treatment.The mean size and appearance of BDT-TTQ NPs were characterized by dynamic light scattering?DLS?and transmission electron microscopy?TEM?,indicating that the nanoparticles had good dispersion in aqueous solution.The excellent biocompatibility of BDT-TTQ NPs was proved by MTT experiment and confocal imaging.We also studied the in vivo photothermal properties,NIR-? fluorescence imaging and tumor ablation of BDT-TTQ NPs,these results proved that BDT-TTQ NPs can achieve high-quality NIR-?a FI and tumor NIR-? PTT.