Design Of New Organic Semiconducting Nanoprobes In Tumor Bioimaging And Therapy Applications

Organic semiconducting dyes have been widely used in light emitting diode(LED)and solar cells in light of their good photostability,excellent thermostability,great light harvesting capabilities and alternative photophysical property.Recently,the researchers have developed a number of medical contrast agents based on organic semiconducting dyes in no-invasion optical imaging applications.In addition,one organic dye can integrate multiple light-activated diagnose and therapy functions(such as fluorescence imaging,photoacoustic imaging,photothermal therapy and photodynamic therapy).Moreover,organic dyes can be easily modified and inoculated by other imaging and therapy function.Thus,the multifunctional theranostic nanoplatforms will be conveniently realized based on organic dyes for precision medicine application.Unfortunately,the imaging resolution and signal-tobackground ratio(SBR)of the presented optical agents haven't been ideal for further precision medicine.Because of high accuracy,deep imaging depth and high resolution of photoacoustic imaging(PAI),fluorescence imaging(FI)in near-infrared window(700-1700 nm,NIR),this work synthesized new organic dyes using these imaging technologies for precision medicine.We proposed some strategies of developing “turn-on” dyes,matching donor(D)and acceptor(A)of D-A polymer and introducing new quinoid polymer to enhance the signals and SBR in the tumor for precise imaging.1.A Tumor-Microenvironment Sensitive “Turn-on” Conjugated Dye for Photoacoustic Imaging Guided Synergetic Photothermal Therapy and Chemotherapy in TumorBased on redox sensitive poly(disulfide)s(PDS)easily broken by high concentration of glutathione(GSH)in the cancer cells,this study designs a theranostic nanoplatform for boosting photoacoustic(PA)signals and drugs delivery in the tumor.The NIR dye(PDI)is introduced to PDS to fabricate drug carrier(PDI-ss-PEG)with “turn-on” PA performance in cancer cells,then the doxorubicin(DOX)is loaded into the amphiphilic PDI-ss-PEG for PA imaging /photothermal therapy(PTT)/chemotherapy theranostic nanoplatform(PDI-ss-PEG@DOX).This nanoplatform is stable in the normal physiological environment.Once entrance the cancer cells and contacting the high concentration of GSH,the PDI-ss-PEG@DOX is disrupted within 5 h and delivers amount of drugs meanwhile the PDI dyes rapidly aggregate by hydrophobic nature for increasing PA signals.With good photothermal effect,the excellent chemo-photothermal synergetic treatment results are demonstrated to be superior to the independent chemotherapy or PTT results in the in vitro and in vivo experiments.This work provides a convenient strategy to realize “turn-on” PA signals in tumor and efficient PTT/chemotherapy synergetic treatment.2.Development of Semiconducting Polymer Nanoparticles for NIR-II Photoacoustic Imaging System Guiding NIR-II Photothermal TherapyThis study introduces a two-acceptor semiconducting polymer structure to reduce the bandgap of polymer for increasing light harvesting capabilities beyond 1300 nm section.With the benzobisthiadiazole(BBTD)and diketopyrrolopyrrole(DPP)as two acceptors,we synthesize a 1300 nm absorption semiconducting polymer nanoparticles(SPNs3).As the promising NIR-II PAI/PTT agent,SPNs3 exhibits a high photothermal conversion efficiency(60%)at 1064 nm and a strong photoacoustic signal at 1280 nm.Furthermore,we use SPNs3 to realize in vivo NIR-II photothermal therapy(PTT)treatment guided by commercial small animal NIR-II photoacoustic imaging(PAI)systems.This work provides an effective strategy to design 1300 nm absorption SPNs with enhanced NIR-II PA signals for commercial NIR-II PAI System Guiding NIR-II PTT.3.New Quinoid Conjugated Polymer for Bright in vivo NIR-II ImagingWe develop quinoid-conjugated polymers to regulate the ICT for brighter NIR-II fluorescence signals.Different with D-A polymers,quinoid structure of the main chains determines the low bandgap character.Interestingly,we find that regulation of the electron-withdrawing groups on quinoid polymers can control the ICT to modulate NIR-II fluorescence,simultaneously having little effect on low-bandgap character.With dilute electron-withdrawing groups,the ICT of quinoid polymers is gradually weakening to generate enhanced NIR-II fluorescence signals.In addition,the promising quinoid polymer probe exhibits obviously over 45% and 100% stronger NIR-II signals than the reported D-A polymer probes(p DA-PEG and PDFT1032)with the 1064 nm LP filters.Furthermore,we demonstrate that the promising quinoid polymer probes are demonstrated to be highresolution and precision in several in vivo NIR-II biomedical imaging applications.This work provides a convenient and effective strategy to solve the contradiction caused by the enhanced ICT of D-A polymers between the low bandgap and strong NIR-II fluorescence intensity to increase NIRII fluorescence signals.