| CT imaging and fluorescent imaging have their respective advantages and disadvantages. The combination of CT and fluorescent imaging can integrate their advantages and contribute to molecular functional imaging and tissue structure imaging simultaneously, for which CT-fluorescent bi-model nano probes are the basic foundation. Currently, common CT-fluorescent bi-model probes were synthesized mainly by combining precious metals with organic florescent dyes or common QDs, but it has a lot of problems in preparation and application. For instance, organic dyes have narrow excitation spectrum, wide emission spectrum, low resistance to photo bleaching, short lighting lifetime and complex operation process. Common QDs are usually toxic for containing toxic heavy metals. As a new kind of NIR QDs, Ag2 S QDs have broad and continuous excitation spectrum, adjustable emission spectrum, NIR-II fluorescent window, anti-photo-bleaching, long fluorescent lifetime, none toxic heavy metals and high biocompatibility, which makes it a potential NIR fluorescent molecule. Iodinate oil has relatively high X-ray attenuation coefficience, and has been used as clinical diagnostic X-ray contrast agent with high biological safety. Therefore, the bi-model nano probe combining Ag2 S QDs with iodinate oil has broad application prospects in bi-model imaging. The main contents of this article are as following:(1) We synthesized DSPE-PEG2000-FA successfully with DSPE-PEG2000-NH2 and folate catalyzed by DCC; We made use of DSPE-PEG2000-FA and other amphiphilic molecules to wrap oil-soluble Ag2 S QDs and iodinate oil together, and prepared Ag2 S QDs-Iodinate Oil@DSPE-PEG2000-FA multifunctional nano probes successfully. TEM and DSL results revealed that the probes were highly dispersed and spherical with diameter about 139.6 nm. In-vitro CT-fluorescent imaging showed that the nano probes' CT HU value increased linearly with its concentration, and NIR fluorescent signal intensity also increased gradually. In all, the probes had CT contrast capabilities and NIR fluorescent imaging capabilities in vitro.(2) We used MTT assay and Colony-Formation Assay to detect the cytotoxicity of the probes. The growth and proliferation of HeLa and MCF-7 cells at short and long term had not been obviously inhibited by the probes at concentration of 25 ?g Ag /mL. Fluorescence, CT and TEM results revealed that the probes could bound to folate receptor on HeLa cell surface specifically and were engulfed by HeLa cells, having abilities in cellular CT-fluorescent imaging. In all, the probes can be used as diagnostic imaging agents targeting some tumors, which can express folate receptors at high level, such as HeLa cell.(3) In-vivo tests showed it had long circulation time and its blood half lifetime was 5.7 hours. And HE staining results showed it did not have obvious disadvantages on normal organs' function in mice. After injecting the probes into mice, blood analysis and liver enzyme activity analysis also revealed indicators of blood condition were hardly influenced and thus the probes were rather safe in vivo. We injected the probes into nude mice bearing HeLa tumors, after 24 h we found the tumor tissues had strong CT and fluorescence enhancement signal, and S/N(signal to noise ratio) between tumor and normal tissue was quite high, and the shape, size and location of tumors could be clearly determined, indicating the probes had good capability in tumor-targeting CT-fluorescent bi-model imaging in vivo. Thus, the nano probes had great potential in CT-fluorescent bi-model imaging.In summary, we have made use of Ag2 S QDs, iodinate oil, DSPE-PEG2000-FA and other amphiphilic molecules to prepare biocompatible Ag2 S QDs-Iodinate Oil@DSPEPEG2000-FA probes, which could target tumor in mice by CT-fluorescent bi-model imaging. This article provided a new method for bi-model imaging designing, in-vivo imaging and tumor-targeting diagnosis. |
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