Development Of Tumor-targeted Long Afterglow/MRI Bimodality Probes For In Vivo Imaging

In the area of in vivo imaging,development of molecular imaging probes with high sensitivity,high specificity and excellent imaging performance is of great significance for diagnosis and monitoring of diseases such as cancer.In recent years,many types of molecular imaging probes have been used for bioimaging.Each molecular imaging mode has advantages as well as disadvantages,for example,long afterglow probes have high sensitivity,high signal-to-noise ratio,but poor spatial resolution.Magnetic resonance imaging probes have high spatial resolution but low sensitivity.In order to improve the efficiency of in vivo imaging,people have combined the two imaging modes to build the long afterglow/magnetic resonance imaging bimodal probes for diagnosis of tumors,but most of these probes still have the following problems:(1)lack of tumor-targeting ability,(2)rigorous preparation conditions and potential biotoxicity due to the use of inorganic afterglow materials doped with heavy metal elements.Long afterglow/magnetic resonance imaging bimodal probes with high biocompatibility,high signal-to-noise ratio,high spatial resolution imaging and tumor-targeting ability have not been reported.Therefore,we chose the organic afterglow system and magnetic resonance contrast agent to build a bimodal probe.Due to the specific combination of targeting ligand c RGD with the αvβ3-integrin which is overpressed on MKN45 tumor cell surface,we introduced c RGD into the probe to achieve its accumulation in the tumor tissues,and then stronger imaging signal could be obtained.This thesis is composed of the following two parts:In the first chapter,we briefly introduce the basic contents of molecular imaging,molecular imaging probes of different modes and multimodal probes.The first part focuses on the concept of molecular imaging and various types of common molecular imaging probes.The second part mainly introduces the application of afterglow imaging probes and magnetic resonance imaging probes.In the third part,the current reported long afterglow/magnetic resonance bimodal molecular imaging probes and their imaging applications are introduced.In the second chapter,the long afterglow system(MEH-PPV and NIR775)was coated in nanoparticles by nanoprecipitation method,and the magnetic resonance contrast agent DTPA-BSA(Gd)and target group c RGD were modified on its surface to construct the long afterglow/magnetic resonance bimodal imaging probe NPS-RGD,which was applied for the specific imaging of tumors.The in vitro results demonstrate that the NPS-RGD has a high r1 relaxivity(15.2 m M-1 s-1),and can emit intense afterglow signal after 808-nm laser irradiation.Cell study results show that the NPSRGD could enter MKN45 tumor cells via αvβ3-integrin-mediated endocytosis and differentiate the αvβ3-overexpressed tumor cells from αvβ3-deficient normal cells.We also verified that the different imaging mode in this work has different detection sensitivity at the cellular level,the long afterglow imaging mode is the most sensitive(detection limit: ~50 cells/μL),while the magnetic resonance imaging mode is the most insensitive.Moreover,the probe NPS-RGD can accumulate in xenograft MKN45 tumors through αvβ3-integrin-mediated delivery,permitting non-invasive imaging of tumors in living mice.This study reveals that the probe NPs-RGD with long afterglow/magnetic resonance bimodal imaging function,which was constructed by nanoprecipitation method,could facilitate the analysis of tumors with good biocompatibility,high sensitivity,high signal-to-noise ratio and high spatial resolution.