聚乙二醇化介孔二氧化硅包裹共轭聚合物用于近红外光学诊疗

doi:10.6023/A24090286

摘要/Abstract

近红外荧光成像及光学治疗技术在生物医学领域受到了越来越多的关注, 为各种疾病的诊疗提供了全新的手段. 近年来, 高性能光学诊疗试剂的开发已成为相关领域的研究热点. 本工作将共轭聚合物包裹在高度聚乙二醇化的介孔二氧化硅中, 获得了高稳定、高亮度、高生物相容的近红外光诊疗试剂. 该材料在近红外一区(NIR-I)和近红外二区(NIR-II)都具有较强的荧光发射, 并且在730 nm激光照射下具有较高的光热转换效率(40.5%)和单线态氧量子产率(5.2%). 利用该材料同时对小鼠进行NIR-I和NIR-II成像能够消除个体差异和随机性误差, 更加准确地比较两种荧光成像模式. 通过皮下肿瘤模型, 发现NIR-I成像能够提供更高的肿瘤-肝脏信号比, 有利于皮下肿瘤的早期诊断和初步定位. 而NIR-II成像具有更高的信噪比和分辨率, 能够更加清晰地描绘肿瘤轮廓且不受动物毛发自发荧光干扰, 在荧光成像指导的手术切除方面更具优势. 此外, 该材料联合了光热和光动力学治疗方式, 在活体抗肿瘤实验中表现出优秀的光学治疗效果.

关键词: 共轭聚合物, 介孔二氧化硅, 近红外二区, 光学诊疗, 荧光增强

The near-infrared fluorescence imaging and phototherapy technologies have garnered increasing attention in the biomedical field, providing novel approaches for the diagnosis and treatment of various diseases. In recent years, the development of high-performance phototheranostic agents has become a research focus in the related fields. This study encapsulated conjugated polymers (CP) within highly polyethylene glycol (PEG)-grafted mesoporous silica nanoparticles (CP@mSiO₂-PEG), resulting in a highly efficient near-infrared phototheranostic agent with high stability, brightness, and biocompatibility. The obtained material exhibited strong fluorescence emission in both the first (NIR-I, 700~900 nm) and the second (NIR-II, 1000~1700 nm) near-infrared regions, along with a high photothermal conversion efficiency (40.5%) and a singlet oxygen quantum yield (5.2%) under 730 nm laser irradiation. Taking advantage of the strong and broad fluorescence emission, simultaneous NIR-I and NIR-II imaging in one living mouse can be achieved to compare the advantages and disadvantages of the two NIR fluorescence imaging modalities. This approach eliminated individual differences and random errors, which can provide a more accurate and reliable result. Through subcutaneous tumor models, it was observed that these highly PEGylated nanoparticles can be efficiently accumulated at the tumor sites after intravenous injection. Performing NIR-I and NIR-II fluorescence imaging with the same tumor-bearing mouse, it was found that NIR-I imaging can provide a higher tumor-to-liver signal ratio, which facilitates the early diagnosis and preliminary localization of subcutaneous tumors. In contrast, NIR-II imaging offers a higher signal-to-background ratio and a higher resolution, which enables clearer delineation of the tumor contour, thus demonstrating greater advantages in fluorescence imaging-guided surgical resection. Additionally, NIR-II imaging can eliminate the interference from the spontaneous fluorescence of the animal fur. Furthermore, the obtained nanoparticles, which integrate photothermal and photodynamic therapy modalities, also exhibiting high phototherapy efficacy for in vivo tumor therapy. The conjugated polymer used here can also be replaced with other desired polymers to achieve other optical applications.

Key words: conjugated polymer, mesoporous silica, NIR-II, phototheranostics, enhanced fluorescence

引用此文

张雨琦, 占辰, 贡祎, 陆峰, 范曲立. 聚乙二醇化介孔二氧化硅包裹共轭聚合物用于近红外光学诊疗[J]. 化学学报, 2024, 82(12): 1226-1233.

Yuqi Zhang, Chen Zhan, Yi Gong, Feng Lu, Quli Fan. PEGylated Mesoporous Silica Coated Conjugated Polymer for NIR Phototheranostics[J]. Acta Chimica Sinica, 2024, 82(12): 1226-1233.

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图/表 7

图1. CP@mSiO2-PEG复合纳米粒子的制备流程及应用示意图

Figure 1. Schematic illustration of the preparation of CP@mSiO2-PEG nanoparticles and their applications

图2. (a) CP@mSiO2-PEG的透射电子显微镜图片; CP@F127和CP@mSiO2-PEG的(b)吸收光谱和(c)近红外一区荧光光谱; (d) CP@F127和CP@mSiO2-PEG的近红外二区荧光光谱图及CP的结构式

Figure 2. (a) TEM image of CP@mSiO2-PEG; (b) Absorption spectra and (c) NIR-I emission spectra of CP@F127 and CP@mSiO2-PEG; (d) NIR-II emission spectra of CP@F127 and CP@mSiO2-PEG, and the chemical structure of the conjugated polymer

图3. CP@mSiO2-PEG水溶液在(a)不同激光功率和(b)不同吸光度下的温度变化曲线; (c)不同功率激光照射下的红外热成像图; (d)材料的光热稳定性; (e)时间和–lnθ的线性拟合曲线; (f) CP@mSiO2-PEG的光动力学性能曲线

Figure 3. Temperature elevation of CP@mSiO2-PEG solution under laser irradiation with different (a) power densities and (b) absorbance; (c) Thermal image of CP@mSiO2-PEG solution under laser irradiation; (d) Photothermal stability characterization of CP@mSiO2-PEG; (e) The linear fitting of the time versus –lnθ; (f) Photodynamic performance of CP@mSiO2-PEG

图4. (a)不同条件下细胞内的活性氧生成情况, 标尺为20 μm; (b)不同浓度CP@mSiO2-PEG及光照后的细胞活性; (c)材料及光照后的细胞活死染色情况, 标尺为200 μm

Figure 4. (a) Generation of reactive oxygen species under different conditions, scale bar: 20 μm; (b) The cell viabilities after incubation with different concentrations of CP@mSiO2-PEG and exposed to laser; (c) Live/dead staining of the cells treated with nanoparticles with and without laser, scale bar: 200 μm

图5. 注射CP@mSiO2-PEG后, 小鼠的(a)近红外一区和(b)近红外二区血管成像图; (c)近红外一区和(d)近红外二区图像中红线上的荧光强度值

Figure 5. (a) NIR-I and (b) NIR-II fluorescence image of the blood vessels after the injection of CP@mSiO2-PEG; Fluorescence intensities across the red lines in the (c) NIR-I and (d) NIR-II images

图6. (a)注射CP@mSiO2-PEG不同时间后, 在近红外一区和近红外二区的小鼠肿瘤荧光成像图; 两种成像模式下, (b)肿瘤部位荧光强度值及(c)肿瘤与肝脏的信号强度比值, 随注射时间的变化

Figure 6. (a) NIR-I and NIR-II fluorescence image of tumor bearing mouse after the injection of CP@mSiO2-PEG; (b) Fluorescence intensities at the tumor site and (c) the signal ratios between the tumor and the liver at different post-injection time under the two imaging modes

图7. 注射CP@mSiO2-PEG不同时间后, 荷瘤小鼠在激光照射下的(a)热成像图片和(b)肿瘤部位的温度曲线; 经不同手段治疗后, 荷瘤小鼠的(c)瘤体积, (d)瘤重, (e)体重及(f)肿瘤组织的H&E染色图片, 标尺为50 μm

Figure 7. (a) Thermal images and (b) the tumor temperature profiles of the tumor-bearing mice under laser irradiation after the administration of CP@mSiO2-PEG; (c) Tumor volumes, (d) tumor weights, (e) body weights, and (f) H&E staining of the tumor tissues after different treatments, scale bar: 50 μm

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