图1 肝癌介入栓塞微球分类

Fig.1 Classification of transarterial embolization microspheres for liver cancer.

图2 磁响应性微球栓塞

Fig.2 Magnetic-responsive embolization microspheres. A: Schematic diagram of embolization of PS/Fe₃O₄@MONs microspheres. The microspheres are fabricated by loading polystyrene/Fe₃O₄ particles onto mesoporous silica microspheres (MONs). B: Scanning electron microscope (SEM) image and elemental mapping of PS/Fe₃O₄@MONs microspheres. Blue, purple, yellow, and red indicate carbon, oxygen, silicon, and iron elements, respectively. C: DSA images before and after embolization with PS/Fe₃O₄@MONs microspheres. The red dotted lines indicate the visualized tumor blood vessel. D: MRI images showing tumor changes on day 0 and day 7 after treatment in the control group, Lipiodol group, Lipiodol+Dox group, PS/Fe₃O₄@MONs group and PS/Fe₃O₄@MONs@Dox group. The red dotted lines indicate the tumor.

图3 声动力栓塞微球

Fig.3 Sonodynamic embolization microspheres. A: Schematic diagram of the sonodynamic embolization process of sonodynamic embolization microspheres. B: Transient air pressure diagrams at different time points inside simulated blood vessels (T1/2 represents half of the acoustic cycle). C: Embolization process of sonodynamic embolization microspheres in the rabbit ear artery under ultrasonic guidance: movement trajectories of 100 μm and 20 μm microspheres during acoustic steering. Image subtraction reveals microsphere size distribution. Red dotted lines indicate the positions for grayscale analysis (The black arrows indicate microspheres, and the multicolored arrows denote acoustic pressure phase gradient). Scale bar=100 μm.

图4 声动力免疫-栓塞微球

Fig.4 Sonodynamic immunological-embolization microspheres. A: Schematic illustration of combined sonodynamic immunotherapy and embolization using gelatin microspheres (Mn-GMSs) loaded with hypoxia-responsive manganese tungstate (MnWOₓ) sonosensitizer nanoparticles. B: Optical microscopy (OM) and scanning electron microscopy images of Mn-GMSs microspheres. C: DSA images of rabbit renal artery and hepatocellular carcinoma blood vessels before and after embolization with Mn-GMSs (The yellow dotted lines indicate the embolized region). CT images of kidneys acquired on days 3, 7, and 21 post-renal artery embolization (blue arrow: right kidney, yellow arrow: left kidney). D: CT images evaluating hepatocellular carcinoma tumor changes on days 0, 7, and 14 after treatment in the control group, GMSs group, Mn-GMSs group, and Mn-GMSs/US group (The yellow dotted lines indicate the tumor).

图5 pH响应性栓塞微球

Fig.5 pH-responsive embolization microspheres. A: Schematic diagram and mechanism of pH-responsive calcium carbonate-alginate (CaCO₃-ALG) embolization microspheres for hepatocellular carcinoma embolization in SD rats. The puncture site is upstream of the ligation point at the distal gastroduodenal artery (yellow arrow). Microspheres are injected via the catheter placed in the hepatic artery (green arrow). B: Characterization of CaCO₃-ALG microspheres. a-c) Optical and scanning electron microscopic images of ALG and CaCO₃-ALG microspheres; d-f) Optical and scanning electron microscopic images of CaCO₃-ALG microspheres. C: Changes in the counts of regulatory T cells (Treg) and CD4⁺ T cells in the tumor microenvironment after embolization with ALG and CaCO₃-ALG microspheres in SD rat liver tumors. D: PET imaging evaluation of tumor changes in SD rat liver cancer after treatment with lipiodol, ALG microspheres, and CaCO₃-ALG microspheres (The yellow arrows indicate the tumor)

图6 射频响应性双价金栓塞微球

Fig.6 Radiofrequency-responsive embolization microspheres. A: Schematic illustration of the preparation of divalent gold colloidal nanoparticle microspheres (dvGC@PNAs) and their synergistic anti-tumor therapy combining radiofrequency ablation (RFA) and transarterial embolization (TAE). B: High-resolution transmission electron microscope images of dvGC particles and dvGC@PNAs embolization microspheres. C: Three-dimensional CT reconstructed images of rabbit renal arteries at different time points after embolization in the Lipiodol group and dvGC@PNAs group. D: Ex vivo thermal imaging comparison of porcine liver tissues in the NS group, dvGCs group, and dvGC@PNAs group at 0, 1, 2, 3, and 4 minutes under radiofrequency current stimulation (0.8 mmol Au/mL, 100 W, 4.0 min).

图7 光响应性栓塞微球

Fig.7 Photoresponsive embolization microspheres. A: Schematic preparation of MnO₂/verteporfin (BPD)-based embolization microspheres (NanoBPD) and their application in liver cancer embolization (The white arrows indicate thrombosis). B: Transmission electron microscopy (TEM) images of MnO₂/BPD and NanoBPD embolization microspheres. C: Tumor changes in mice at different time points after NanoBPD embolization. a-i) MRI observations of tumor evolution at different times post-embolization (The red frames and the arrows indicate the tumor; magnified details and corresponding pathological images are presented). j) Magnetic resonance signal-to-noise ratio (SNR) of tumor and normal liver tissues at 0, 0.5, 4, 8, 24, 48h after NanoBPD embolization (P<0.0001).

图8 Pickering乳液栓塞系统

Fig.8 Pickering emulsion embolization system. A: Preparation principle of calcium phosphate nanoparticle-based Pickering emulsion microspheres loaded with L-arginine (L-Arg@CaPL) and schematic diagram of liver cancer embolization in SD rats. B: TEM and SEM images of calcium phosphate nanoparticles, photograph of L-Arg@CaPL emulsion, and elemental distribution of Ca (blue), P (red), and O (yellow) in microspheres. Scale bar: 1 μm. C: MRI-based evaluation of tumor changes in SD rat liver cancer on day 0 and day 14 after embolization with Lipiodol, CaLP, and L-Arg@CaPL (The white dotted lines indicate the tumor).

图9 基于Janus颗粒的自适应碘油液滴微球栓塞系统

Fig.9 Janus particle-engineered structural lipiodol droplets embolization system. A: Schematic diagram of embolization with Janus particle-based lipiodol droplet microspheres. B: Photographs (upper) and optical microscopic images (lower) of Janus particle-based lipiodol droplet microspheres. C: Distribution of Janus particle-based lipiodol droplet microspheres in decellularized liver blood vessels of SD rats. D: Evaluation of renal artery embolization efficacy in rabbits. a) In vivo DSA images of rabbit renal arteries before embolization and on day 14 after treatment with 8spheres®, lipiodol, and Janus particle-based lipiodol droplet microspheres (The red dotted lines indicate renal outline before embolization, and the green dotted lines indicate renal outline after embolization). b) DSA images showing the embolization effects of the three groups on day 14 post-operation. The red dotted lines indicate the pre-embolization renal outline.

图10 肿瘤血管适应性、粘附性和可吸收性(3Asphere)栓塞微球

Fig.10 Tumor vessel-adaptive, adhesive, and absorbable (3Asphere) embolization microspheres. A: Schematic diagram of rabbit liver cancer embolization with hyaluronic acid derivative-based 3Asphere microspheres. B: Fluorescence and scanning electron microscopic images of 3Asphere microspheres. Scale bar: 100 μm. C: Renal artery embolization effect of 3Asphere microspheres in rabbits observed via DSA imaging. D: Imaging evaluation (upper) and 3D reconstruction (lower) of rabbit renal arteries before embolization and on days 3, 7, 14, and 28 after 3Asphere embolization under CT scanning. E: CT imaging assessment of tumor changes in rabbit liver cancer before embolization and on day 14 post treatment with EPI-CalliSpheres® and EPI 3Asphere microspheres (The yellow dotted lines indicate the tumor).