Tumor Microenvironment And Biomarker-dual Targeted Molecular Probe For Tumor Imaging Studies

Cancer is one of major diseases that threaten human health,with the characteristics of high morbidity and high mortality.Cancer not only seriously affects people’s quality of life,but also occupies a lot of medical resources and brings a huge economic burden to the sustainable development of our society.Developing malignant tumor-specific molecular probes is the key to personalized precision diagnosis and treatment of malignant tumors,and also the frontier field of analytical chemistry.Nucleic acid aptamers generated by SELEX technique are a class of oligonucleotide sequences that can bind to the target with specificity and high affinity.Based on chemical solid-phase synthesis,precise modification,and programmable designability,nucleic acid aptamers as molecular tools have been widely used in the diagnosis and treatment of malignant tumors.However,the targeted enrichment ability and retention time of nucleic acid aptamers in malignant tumors are limited,which restricts the further application of nucleic acid aptamers.By targeting biochemical characteristics such as low pH or hypoxia in the tumor microenvironment,tumor-targeted probes(e.g.,p HLIP)can efficiently accumulate in tumor,but with limited ability to recognize tumor cells.Based on the idea that the performances of aptamer probes and tumor-targeted probes are mutually complementary,we herein proposed a tumor microenvironment and biomarker-dual targeted molecular probe by integrating aptamer and p HLIP,and explored its application in tumor imaging.The specific content includes the following two parts:In Chapter 2: Two tumor microenvironment and biomarker-dual targeted molecular probes(XQ-2d-p HLIP and Sgc8-p HLIP)were prepared by conjugating DBCO-labeled aptamer with azide-labeled p HLIP via click chemistry reaction.The resulting dual targeted molecular probes were purified by HPLC,and characterized by gel electrophoresis and MS.Final,the molecular probes were quantitated by UV-vis spectroscopy.In Chapter 3: The recognition ability of XQ-2d-p HLIP and Sgc8-p HLIP on cancer cells was first investigated and compared to their controls(aptamer and p HLIP).Then the retention of the dual targeted molecular probes on cells were analyzed.Final,we preliminarily investigated the targeting ability of dual-targeting molecular probes in tumor-bearing mice.The results of the experiments show that the tumor microenvironment and biomarker-dual targeted molecular probes have better tumor enrichment and retention ability,and it is expected to provide a new molecular probe for the precise diagnosis and treatment of malignant tumors.