Design,Preparation And Bioevaluation Of Inorganic Nano-Probes For ¹⁹F MRI-guided Breast Cancer Theranostics

In 2020,breast cancer replaced lung cancer as the most prevalent cancer in the world.The key factors to improve the survival rate of breast cancer are early detection,early diagnosis,and early treatment.Compared with other imaging techniques,MRI has excellent soft-tissue imaging function and unlimited depth of tissue penetration,so it is widely used in clinical and scientific research.The advantages of non-conventional 19F MRI,which has no endogenous background signal make it lore attractive for hotspot imaging with a higher signal-to-noise ratio and higher sensitivity.Combined 1H MRI/19F MRI shows promising potential in the detection of breast cancer with fluorinated theranostic agents.Inorganic nanomaterials can be used as a nanosensor for in vivo imaging by controlling chemical composition,crystallinity,size,shape,surface properties,and physical properties.This study aims to develop highly sensitive and multifunctional fluorinated nanoprobes for 19F MRI based on the unique physical and chemical properties of inorganic nanomaterials and evaluated their feasibility for image-guided breast cancer theranostics.Following are the main research methods and results:(ⅰ)We developed a novel 19F MRI nanoprobe and applied it to the detection and treatment of breast cancer.2D Pd@Au NPs were introduced into the FY-NCs to construct the FY-Pd@Au nano-metallacages(FY-Pd@Au NCs)for 19F MRI/CT/PAIguided cancer combined phototherapy.2D Pd@Au NPs were inlaid in FY-NCs to realize the integration of PTT and type Ⅰ PDT.And the 19F MRI property of FY-NCs can be able to collaborate with the CT/PA imaging function of 2D Pd@Au NPs.All of these imaging properties were kept well after intratumor injection.Under the 808 nm laser irradiation,the FY-Pd@Au NCs can efficiently induce the cell apoptosis in vitro,and completely ablate the tumor in 4T1 tumor-bearing Balb/c mice by the synergetic performance of PTT/PDT without relapse and obvious side effects.(ⅱ)To further improve the fluorine signal of FY-NCs for in vivo 19F MRI furthermore,we redesigned a probe FY-MnO2 NCs to enhance fluorine signal.MnO2 was reduced by glutathione(GSH)in the tumor microenviro1ment to release Mn3+,which could enhance the 19F MRI signal-to-noise ratio.The results show that the probe had excellent GSH responsiveness and great 19F MRI signal,and is suitable for GSH 19F MRI imaging of tumors.(ⅲ)The efficacy of FY-MnO2 NCs in the treatment of breast cancer in tumor-bearing mice was evaluated,and the specific mechanism of manganese ion in tumor treatment was further explored.In the tumor environment,MnO2 was reduced by GSH to bivalent manganese,which could not only enhance the expression of tumor STING protein but also produce ROS in a Fenton-like reaction in an acidic environment,which significantly enhanced the effect of ROS produced by FY-NCs on the tumor.Based on this,this study further explored that FY-MnO2 NCs inhibited tumor growth mainly by activating the STING signaling pathway in the tumor,laying a better foundation for the development of more sensitive and more water-soluble 19F MRI probe for the diagnosis and treatment of breast cancer.