Synthesis And In Vitro Performance Of Bifunctional T₁-MR/Fluorescence Imaging Probes Using Low DP Narrow Molecular Weight Distribution Chitosan As Carrier

The early diagnosis of disease has great significance to develop individualized treatment, reduce the complications and promote the functional recovery of patients. Magnetic Resonance Imaging (MRI) is a noninvasive and tomographic technique with high spatial resolution in tissues contrast, which holds great promise for disease diagnosis in clinic. However, it has lower sensitivity, which makes it hard to get detailed biological information in the process of diagnosis. On the contrary, Optical Imaging (OI) has higher sensitivity with lower resolution. The combination of both MRI and 01 to form dual-mode imaging technique makes it come true that we can obtain detailed information in anatomy and biology. And the technology has been widely concerned in the area of biomedical research. In this work, we used low degree of polymerization (DP) and narrow molecule weight distribution chitosan (hereafter referred to as the Low-Narrow Chitosan) as a carrier to synthesize two kinds of compounds with magnetic resonance relaxation and fluorescence properties, both of which could be used as a potential magnetic resonance (MR)/fluorescence bifunctional imaging probe. The main content is illustrated as follows:1. Introduce the emergence background of multifunctional imaging probe and the current research status of MRI/OI bifunctional imaging probe.2. Gd-based P1 type bifunctional probe (Gd[DTPA/C1-LNCS6]) was synthesized by using the Low-Narrow Chitosan (LNCS6, DP=6) as a carrier,7-hydroxyl-8-formylcoumarin (Cl) as the chromophore, diethylenetriaminepentaacetic acid (DTPA) as the complexing agent of Gd3+. The products were characterized by FTIR and GFC. The results showed that the molar ratio of LNCSn, C2 and DTPA was 1:1:1. The fluorescence and magnetic resonance relaxation properties of complex Gd[DTPA/C1-LNCS6] were studied in vitro and the thermodynamic effect between the complex and bovine serum albumin (BSA) was also investigated. The statistics showed that Gd[DTPA/C1-LNCS6] was a fine-performance MRI contrast agent with excellent optical properties. And it has a moderate binding intensity when combined with BSA, which could be further studied in vivo.3. To further study the impact of DP of Low-Narrow Chitosan on the performance of probe, a series of Gd-based P2 type bifunctional probes (Gd[DTPA/C2-LNCSn], n=6,8,11) were synthesized by using 4-methyl-6-hydroxyl-7-formylcoumarin (C2) as the chromophore, DTPA as the complexing agent of Gd3+, the Low-Narrow Chitosan with different DP (LNCSn, n=6,8,11) as a linker. The products were characterized by FTIR and GFC. The results showed that the molar ratio of LNCS6, C1 and DTPA was 1:1:1. The UV-Vis, fluorescence and magnetic resonance relaxation properties of complex Gd[DTPA/C2-LNCSn] were studied in vitro and the thermodynamic effect between the complex and bovine serum albumin (BSA) was also investigated. The statistics showed that Gd[DTPA/C2-LNCSn] had both fine magnetic resonance relaxation and fluorescence properties. And it has a moderate binding intensity when combined with BSA. With the increase of molecular weight of Low-Narrow Chitosan, the fluorescence intensity and magnetic resonance relaxation properties were improved distinctly.