Multifunctional Organic Small Molecular Probe For Tumor Imaging And Therapy

Cancer(malignant tumor)is a serious endanger to human life and health.The theranostics strategy combined imaging and treatment functions in a single complex,provides real-time tumor detection,drug accumulation,and imaging-guided precision cancer therapy and prognosis evaluation.Organic small molecular drugs(molecular weight is less than 1000)with the advantages of simple and controllable molecular structure,easy production in large scale,high stability and easy storage,high effective ingredients,account for the majority of the drug market.In this thesis,we developed a series of organic small-molecule theranostic probe,which activated by tumor microenvironment(e.g.,pH,thiol,hypoxia,etc)and emerged integration of tumor diagnosis and treatment.These small-molecule theranostic probe may have important implications for tumor deep-tissue NIRF/PA imaging and precision phototherapy in vivo.It also provided a new strategy to the design and development of novel organic small molecular drugs.The main contents are as follows:(1)Tumor-targeted small molecule for dual-modal imaging-guided phototherapy upon near-infrared excitation.We have successfully developed a multifunctional theranostic small-molecule probe IR-PY integrating tumor targeting,pH sensing,and photothermal therapy.IR-PY realized NIRF/PA dual-modal imaging and effective photothermal therapy in tumor bearing mice.Through a facile synthesis with integrated high-contrast imaging and highly-effective therapeutic functions,such a biocompatible small-molecule theranostic probe is promising for tumor-targeted precision detection and therapy.(2)Dual-responsive molecular probe for tumor targeted imaging and photodynamic therapy.We developed a small-molecule theranostic probe(RhoSSCy),which exhibited dual-responsive to both thiols and pH.RhoSSCy showed intrinsic preferential tumor accumulation,NIRF/PA dual-modal imaging,NIR-sensitizing PDT activities and effective photodynamic therapy in tumor bearing mice.The well-defined RhoSSCy could provide the complementary information for accurate imaging-diagnosis,imaging-guided phototherapy and curative effect assessment of tumor.These results highlighted the potential of RhoSSCy as a versatile theranostic agent to tumor targeted sensing and imaging-guided PDT.(3)Hypoxia-triggered single molecule probe for high-contrast NIR-II FL/PA tumor imaging and robust photothermal therapy.we developed a hypoxia-triggered and NTR enzyme-response single molecule probe for high-contrast NIR-II FL/PA tumor imaging and hypoxia-activated photothermal therapy.The IR1048-MZ molecular probe itself has a very weak NIR-II fluorescent and photoacoustic signal.However,after activated in hypoxic tumors,the probe emitted intensive NIR-II FL/PA signal,which provided more accurate and more deep-tissue imaging on the position and boundary of tumors.Importantly,the hypoxia-activated photothermal therapy of IR1048-MZ exhibited outstanding phototherapy efficacy with rapid increases in temperature and resulted in ablation of tumors with no recurrence.Therefore,the versatile IR1048-MZ probe was not only an activable NIR-II FL/PA dual-modality imaging probe to hypoxia response rapidly,selectively,and sensitively,but also as a robust small molecular photosensitizer for high-efficency photothermal therapy.By tracing the activity of nitroreductase-NTR,IR1048-MZ may be a promising contrast agent and theranostic formulation for hypoxia-related diseases(such as tumor,inflammation,stroke,and cardiac ischemia).