图1 UCNPs用于多模态成像

Fig. 1 Upconversion nanoparticles (UCNPs) assisted multimodal imaging

图2 UCNPs的组成、UCL和荧光发射能级图[31-32]

Fig. 2 Composition, upconversion luminescence (UCL) emissions and fluorescent energy-level diagrams of the UCNPs[31-32] (a) Schematic diagram of UCNPs; (b) Typical UCL emissions of Yb3+-Er3+ and Yb3+-Tm3+ co-doped UCNPs under 980 nm excitation[31]; (c) Partial energy-level diagrams of lanthanide ions[32]

图3 UCNPs的制备方法

Fig. 3 Preparation methods of UCNPs

图4 UCNPs的表面修饰和改性方法

Fig. 4 Modification methods of UCNPs

图5 PEI/NaYF4纳米颗粒用于人卵巢癌细胞和人结肠腺癌细胞的成像照片[44]

Fig. 5 Images of PEI/NaYF4 nanoparticles for human ovarian carcinoma cells and human colon adenocarcinoma cells[44] Bright field (left), confocal (middle), and superimposed (right) images of live human ovarian carcinoma cells (OVCAR3, top row) and human colon adenocarcinoma cells (HT29, bottom row). Nanoparticles were surface modified with folic acid.

图6 免疫荧光标记细胞的超分辨成像[50]

Fig. 6 STExD (stimulated-emission induced excitation depletion) imaging of immunolabelled subcellular filaments[50] (a) Fluorescence image under 740 nm Gaussian beam excitation and (b) differential interference contrast image of actin protein in HeLa cells immunolabeled with phalloidin conjugated NaYF4: Nd nanoparticles; (c, f) Magnified areas and (d, g) super-resolution images under co-irradiation with 740 nm Gaussian beam and 1064 nm donut-shaped beam from white-dotted squares in (a); (e, h) Analyses of line profiles, indicated with white arrows in (c, d), as well as in (f, g), respectively; (i) Photon counts recorded with and without co-irradiation of 1064 nm donut-shaped beam with insets showing the corresponding images with the measured positions marked with white crosses

图7 含镧系元素Yb (a)和Lu (b)的UCNPs用作CT成像造影剂[56-57]

Fig. 7 UCNPs containing lanthanide elements Yb (a) and Lu (b) used as CT imaging contrast agents[56-57] (a) In vivo CT imaging after intravenous injection of 1 mL UCNPs (Yb: 70 mg·mL-1), with photos showing heart and liver, spleen and kidney, and three-dimensional CT images, respectively[56]; (b) Application of NaYF4: Nd3+@NaLuF4@PDA used for CT imaging, with photos showing X-ray images and HU values of NP@PDA18 nanocomposites and iodoxazole aqueous solution with different concentrations, and X-ray CT images of HeLa tumor bearing nude mice before and after intratumoral injection of 100 μL of NP@PDA18 solution (3 mg·mL-1)[57]

图8 UCNPs用于UCL/MRI双模态成像[66]

Fig. 8 Application of UCNPs in UCL/MRI dual-modality imaging[66] (a) In vivo T1-weighted MRI of kidneys of mice (as arrowed) before and after the intravenous administration of NaGdF4@poly-L-lysine (PLL) nanoparticles; (b) Chemical exchange saturation transfer (CEST) contrast difference map between pre/post injection following radio frequency (RF) irradiation at 3.0 μT, showing the kidney signal in color on the grayscale image to highlight the effect; (c) In vivo T1-weighted MRI of brain tumor (as arrowed) after the intravenous administration of NaGdF4@PLL nanoparticles; (d) CEST contrast difference map between pre/post injection at 3.0 μT, showing the brain ventricle signal in color on the grayscale image to highlight the effect; (e) Merged image of (c, d); (f) H&E staining of the brain tumor tissue; (g) Immunohistochemical staining of the brain tumor tissue, showing the positive expression of glial fibrillary acidic protein

图9 NaYF4: Yb/Er@NaGdF4@金属有机框架(MOFs)@阿霉素(DOX)的制备及其UCL/MRI应用[67]

Fig. 9 Preparation and UCL/MRI application of NaYF4: Yb/Er@NaGdF4@metal-organic frameworks (MOFs) @doxorubicin (DOX)[67] (a) Schematic illustration of NaYF4: Yb/Er@NaGdF4@MOFs (UCMOFs) for dual pH-response drug release, UCL imaging and MRI; (b) Confocal fluorescence images of HeLa cells after incubation with NaYF4: Yb/Er@NaGdF4@MOFs@DOX (UCMOFs@D) for 2, 4 and 6 h at 37 ℃, with purple indicating released anticancer drug DOX, green and red indicating UCL (scale bar: 20 µm)

图10 Lip-FNPs-Gd纳米复合材料的制备及其在T1-T2型MRI/UCL双模态成像中的应用[68]

Fig. 10 Preparation of Lip-FNPs-Gd nanocomposite and its application in T1-T2 MRI/UCL dual-modality imaging[68] (a) Schematic illustration of preparation of Lip-FNPs-Gd nanocomposites and ferrocene/selenium-mediated applications in T1-T2 MRI/UCL multimodal imaging and NIR-promoted Fenton therapy of tumors; (b) UCL, (c) T1- and T2-weighted MRI of AGS tumor-bearing mouse for different periods of time; Corresponding T1 (d) and T2 (e) intensity analysis of tumor MRI in (c)

图11 双光敏剂二氢卟吩e6(Ce6)和孟加拉玫瑰红(RB)结合形成的MOF@UCNP用于MRI/UCL双模态成像[69]

Fig. 11 MOF@UCNP formed by combination of dual photosensitizers chlorin e6 (Ce6) and rose Bengal (RB) used for MRI/UCL dual-mode imaging[69] (a) Schematic illustration of fabrication process and operation for imaging-guided photodynamic therapy (dual photosensitizers of Ce6 and RB loaded into MOF nanoparticles and further combined with NaGdF4: Yb,Er@NaGdF4: Nd/Yb via electrostatic interaction to form MOF@UCNP (denoted as CR@MUP)); (b) Fluorescence images of 4T1 tumor-bearing mice at different time after intravenous injection of CR@MUP with white circles showing the tumors; (c) T1-weighted MR images and T1 relaxation curves of CR@MUP; (d) T1-weighted MR images with white circles showing the tumors; (e) Quantification analysis of MR signals of 4T1 tumor-bearing mice treated with CR@MUP

图12 MUCNPs@BPNs-Ce6复合纳米颗粒在T1、T2加权MRI中的应用[72]

Fig. 12 Application of MUCNPs@BPNs-Ce6 in T1- and T2-weighted MRI[72] (a) Linear correlation between longitudinal relativities (r1) and equivalent Mn concentrations of MUCNPs@BPNs-Ce6 at pH 6, with insets showing T1-weighted MR images of MUCNPs@BPNs-Ce6 solution at various Mn concentrations; (b) Linear correlation between longitudinal relativities (r2) and equivalent Fe concentrations of MUCNPs@BPNs-Ce6, with insets showing T2-weighted MR images of MUCNPs@BPNs-Ce6 solution at various Fe concentrations; (c) Blood time activity curve for MUCNPs@BPNs-Ce6 by measuring Fe concentration; (d) In vivo MR images of the tumor of mice before and after injection with MUCNPs@BPNs-Ce6 for 24 h; (e) T1-weighted MR signals in the tumor before and after injection with MUCNPs@BPNs-Ce6 for 24 h; (f) Biodistribution results of HeLa tumor-bearing mice before and after injection with MUCNPs@BPNs-Ce6 in MRI for 24 h; (g) In vivo fluorescence images of HeLa tumor-bearing mice before and after injection with MUCNPs@BPNs-Ce6 for 24 h; (h) Ex vivo fluorescence images of organs and tumor after injection with MUCNPs@BPNs-Ce6 for 24 h; (i) In vivo ultrasonic imaging of HeLa tumor-bearing mice after injection with MUCNPs@BPNs-Ce6 for different time

图13 NaYF4: Yb, Er@mSiO2@Ce6&α-酮戊二酸&GOx@mMnO2@HA(UCAGMH)纳米平台在乳腺肿瘤治疗中的应用[73]

Fig. 13 Schematic illustration of therapy strategy of NaYF4: Yb, Er@mSiO2@Ce6&α-ketoglutaric acid&GOx@mMnO2@HA (UCAGMH) nanoplatforms for breast tumors[73] (a) Therapeutic mechanism of UCAGMH in the mouse breast tumor model; (b) Key role that UCAGMH plays in MRI, CT and FI for therapy guidance in which HA can target CD44 receptors and induce nanoparticles to enter cells through phagocytosis

图14 FYH-PDA-DOX纳米颗粒用于UCL/CT/MRI多模态成像引导的光热治疗(PTT)-化学免疫治疗[77]

Fig. 14 FYH-PDA-DOX nanoparticles used for photothermal therapy (PTT)-chemo-immunotherapy with multimodality UCL/CT/MRI guidance[77] (a) Preparation process of FYH-PDA-DOX complex; (b) Schematic illustration using FYH-PDA-DOX for PTT-chemo-immunotherapy by combining immunogenic cell death (ICD)/ immune checkpoint blockade (ICB) with UCL/CT/MRI guidance; (c) 3D rendering of CT imaging and their corresponding coronal images of mice after injection of FYH-PDA-DOX solutions at timed intervals; (d) T2-MRI of mice before and after injection of FYH-PDA-DOX solutions; (e) Fluorescence images of excised tumors and major organs

图15 RBC-UCNPs纳米颗粒的制备(上)及其在小鼠三基因乳腺癌中的MRI、UCL和PET成像(下)[79]

Fig. 15 Preparation (up row) and application of MRI, UCL and PET imaging (low row) in mice carrying three gene breast cancer of RBC-UCNPs nanoparticles[79]