Bi2S3-SiO2 NRs/二氧化硅涂層硫化鉍納米棒多模態(tài)顯影劑可用于胃腸道GI成像技術(shù)

利用硫酸鋇懸浮液作為X光顯影劑用于小腸成像，由于其自身具備的非降解及其他一些不理想的特點(diǎn)使其在胃腸道穿孔及腸道結(jié)構(gòu)觀測方面受到很大限制；其他常用的胃腸道顯影劑便是碘代分子，但因其本身X射線吸收率較低，所以通常需要大劑量使用才能達(dá)到理想的效果，這常常會(huì)使病人產(chǎn)生碘過敏性反應(yīng)。

制備得到二氧化硅涂覆的硫化鉍納米棒（Bi2S3@SiO2 NRs）作為多模態(tài)顯影劑用于胃腸道的無侵害性實(shí)時(shí)成像以及直接觀測其在胃腸道下部的流經(jīng)過程（Scheme 1）。經(jīng)二氧化硅包覆后，在胃及小腸中，Bi2S3@SiO2 NRs展現(xiàn)出非常好的水溶性，生物相容性以及穩(wěn)定性。通過TEM可以看出，Bi2S3 NRs寬約10 nm，長約50 nm，元素分析譜圖顯示成功制備得到高純度的Bi2S3 NRs（Fig. 1），經(jīng)二氧化硅涂覆后，Bi2S3@SiO2 NRs呈現(xiàn)單分散性，SiO2殼層厚度約為6 nm（Fig. 2）。

Scheme 1 Schematic illustration of the preparation of Bi2S3@SiO2 NRs for bimodal CT/PAT imaging of the GI tract principle based on the unique properties of Bi2S3@SiO2 NRs。

Fig. 1 Characterization of Bi2S3 NRs. (A) HAADF-STEM image and (B) HRTEM image of Bi2S3 NRs prepared by the solvothermal method. (C) Corresponding element mapping for Bi and S of the as-prepared Bi2S3 NRs. (D) EDS of the as-prepared Bi2S3 NRs.

Fig. 2 Characterization of Bi2S3@SiO2 NRs. (A) TEM image and (B) HRTEM image of as-prepared Bi2S3@SiO2 NRs. Inset: HAADF-STEM image of Bi2S3@SiO2 NRs. (C) Corresponding element mapping for Bi, S and Si of Bi2S3@SiO2 NRs. (D) EDS of Bi2S3@SiO2 NRs.

通過CT成像分析發(fā)現(xiàn)，隨著Bi₂S₃@SiO₂ NRs濃度增加，其HU值明顯增加，相同濃度下的HU值明顯高于硫酸鋇，PAT信號(hào)隨濃度增加也呈線性增長關(guān)系（Fig. 3）。

Fig. 3 CT and PAT phantom images of Bi2S3@SiO2 NRs with different concentrations in vitro. (A) Plot of Hounsfield units (HU) values and of Bi2S3@SiO2 NRs and BaSO4 suspension versus the sample concentrations and CT phantom images of Bi2S3@SiO2 NRs and BaSO4 suspension samples with different concentrations. (B) Plot of the photoacoustic signal versus Bi2S3@SiO2 NRs concentrations and PAT phantom images of Bi2S3@SiO2 NRs aqueous solutions with different concentrations.

對(duì)Bi2S3@SiO2 NRs的生物相容性進(jìn)行檢測，發(fā)現(xiàn)16HBE與Bi2S3@SiO2 NRs共培養(yǎng)24 h后并未顯示出明顯的毒性，并且該粒子進(jìn)入秀麗隱桿線蟲體內(nèi)后對(duì)其壽命也沒有明顯的影響，這就說明Bi2S3@SiO2 NRs具有非常好的生物相容性（Fig. 4）。

Fig. 4 Biosafety assessment of Bi2S3@SiO2 NRs by the C. Elegans model. (A) Bright field image of the NRs distribution in the GI tract of C. Elegans. Worms feed on NGM plates with Bi2S3@SiO2 NRs (1000 μg mL?1) transferred onto an agar pad after 1 h. (B) The distribution of food containing Bi2S3@SiO2 NRs (red arrows) in the intestine of the worm’s tail. (C) Effects of Bi2S3@SiO2 NRs with different concentrations on body length of C. Elegans. (D–H) Effects of Bi2S3@SiO2 NRs treatments on the accumulation of lipofuscin in age-synchronized worms. Representative fluorescent images of worms fed with 0, 1, 10, 100 and 1000 μg mL?1 Bi2S3@SiO2 NRs, respectively.

Bi2S3@SiO2 NRs以口服的方式進(jìn)入BALB/c裸鼠體內(nèi)，通過CT及PAT對(duì)Bi2S3@SiO2 NRs進(jìn)行實(shí)時(shí)成像追蹤，發(fā)現(xiàn)該粒子通過胃腸道漸漸進(jìn)入小腸較后以糞便的形式排出體外，該過程中對(duì)胃腸道的功能沒有明顯的損傷，說明Bi2S3@SiO2 NRs對(duì)組織無侵入性損傷（Fig. 5, 6, 7）。

Fig. 5 CT imaging of the GI tract in vivo. In vivo X-ray CT imaging of the GI tractin BALB/c nude mice at different intervals after oral administration of Bi2S3@SiO2 NRs.

Fig. 6 Enlarged images of CT images of the GI tract of mice 30 min post oral administration of Bi2S3@SiO2 NRs.

Fig. 7 PAT imaging of the GI tract in vivo. PAT cross-sectional image of the GI tract of BALB/c nude mice at different intervals after oral administration of Bi2S3@SiO2 NRs: stomach (ST), small intestine (SI) and large intestine

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