Synthesis Of Conjugated Polymer Optical Diagnostic Agents For Tumor Therapy

Phototherapy,including photodynamic and photothermal therapy,has been widely used in the treatment of cancer,which is a new type of cancer treatment with non-invasive and toxic side effects.However,single phototherapy technique has limitations,such as tumor hypoxia resulting from the tissue oxygen consumption for PDT and requried high power density for PTT.In addition,the conventional NPs coated conjugated polymer is injected through the tail vein;which has a problem of easy discharge,systemic toxicity,and low tumor enrichment in the body.There limits its clinical application.In this paper,the zwitterionic polymer is introduced into the conjugated polymer to improve water solubility and photodynamic effects.Then,a polymer is designed by adjusting the structure for the donor and acceptor,and it is then coated in hydrogel for NIR-II imaging and photothermal treatment.The specific contents of this paper are as follows:?1?Synthesis of theranostic get for photoacoustic imaging/photothermal/photodynamic Therapy:Atom transfer radical polymerization and modified with a sulfonic acid group were used in sequence to prepare PDS-PDI.And PDS-PDI quickly self-assembled into nanoparticles with hydrophobic PDI segments as the core and hydrophilic zwitterionic polymer PDS as the shell through strong?-?and hydrophobic interactions in PDI.The zwitterionic group of PDS-PDI not only greatly increased the water solubility of the polymer(up to 24 mg mL^-1),but also improved the efficacy of reactive oxygen species singlet oxygen?¹O₂?.PDS-PDI has a relatively uniform particle size?75±5 nm?,good near-infrared absorption?600-800 nm?,and a molar extinction coefficient of1.125 L g^-1 cm^-1 at 660 nm.The prepared PDS-PDI polymer presents high photothermal conversion efficiency?40%?and efficient singlet oxygen quantum yield?16.7%?under the 660 nm laser irradiation.Meanwhile,PDS-PDI has the strongest photoacoustic signal at 710 nm offering real-time monitoring in tumor sites.In addition,the zwitterionic polymer PDS-PDI has been shown to have excellent cancer therapeutic effects by in vitro and in vivo experiments.?2?Synthesis of theranostic for NIR-II imaging/photothermal therapy:The semiconducting polymer PDPPBT was synthesized via Stille polymerization between diketopyrrolopyrrole-dithiophene trimethylstannyl?DPPDT?and benzothiadiazole-dithiophene dibrominate?BTDT?,then by using the amphiphilic polymer Pluronic F-127 as a stabilizer to prepare the nanoparticles?NPs-DB?.NPs-DB has a particle size of 125±5 nm and good near-infrared absorption,and the extinction coefficient is 26.16 L g^-1 cm^-1 at 930 nm.The prepared NPs-DB presented high photothermal conversion efficiency?58.2%?under the 915 nm laser at the power density of 0.5 W cm^-2.In addition,NPs-DB had high-intensity NIR-II fluorescence signals with a maximum emission of 1082 nm and an imaging depth of up to 8 mm.And the NPs-DB was loaded into the hydrogel Gel-BOB-Fru to obtain a hydrogel Gel-DB.More than 73%of NPs-DB was released within 36 h of incubation from the hydrogel?Gel-DB?in vitro and the release time in vivo is up to 21 days.Finally,the hydrogel Gel-DB achieved long-term NPs-DB release,NIR-II imaging and photothermal therapy in the tumor site.