Biofunctionalized Hybrid Magnetic Gold Nanoparticles as Catalysts for Photothermal Ablation of Colorectal Liver Metastases.
Biofunctionalized Hybrid Magnetic Gold Nanoparticles as Catalysts for Photothermal Ablation of Colorectal Liver Metastases.
复制标题
DOI：
10.1148/radiol.2017161497
复制
发表时间：
2017-07
期刊：
影响因子：
19.7
通讯作者：
S. White;Dong‐Hyun Kim;Yang Guo;Weiguo Li;Yihe Yang;Jeane Chen;V. Gogineni;A. Larson
中科院分区：
文献类型：
--
作者：
S. White;Dong‐Hyun Kim;Yang Guo;Weiguo Li;Yihe Yang;Jeane Chen;V. Gogineni;A. Larson
目的证明抗MG 1标记的杂化磁性金纳米颗粒（HNP）在结直肠癌肝转移灶的光热消融（PTA）中作为催化剂，从而增加消融范围。材料和方法所有实验均在机构动物护理和使用委员会的批准下进行。合成了与抗MG 1单克隆抗体缀合的治疗和诊断多功能HNP，并测定了偶联效率。将5 × 106个大鼠结直肠癌肝转移细胞系细胞植入19只Wistar大鼠肝脏。根据注射将大鼠分为三组：抗MG 1偶联的HNP（n = 6）、仅HNP（n = 6）和仅细胞（对照组，n = 7）。在注射前、注射后即刻和注射后24小时获得逐体素R2和R2* 磁共振（MR）成像测量值。然后用激光功率为0.56 W/cm 2的光纤耦合近红外（808 nm）二极管激光器进行PTA 3分钟，同时测量温度变化。用苏木精-伊红染色评估肿瘤的坏死。采用电感耦合等离子体质谱法分析器官，以评估生物分布。采用单因素方差分析和事后分析比较疗效和肿瘤坏死面积的差异。结果偶联效率为22 μg/mg（55%）。输注前和输注后24小时的T2（重复测量方差分析，P = 0.025）和T2*（P <0.001）测量值之间存在显著差异。抗MG 1 HNP组和仅HNP组之间的T2* 测量值也存在显著差异（P = 0.034）。抗MG 1涂层HNP、HNP和对照组中PTA的平均温度±标准差分别为50.2°C ± 7.8、51°C ± 4.4和39.5°C ± 2.0。电感耦合等离子体质谱显示显着的肿瘤靶向和脾隔离。抗MG 1包被的HNP组、HNP组和对照组的平均肿瘤坏死百分比分别为38% ± 29、14% ± 17和7% ± 8（P = 0.043）。结论靶向单克隆抗体偶联HNP可作为光热消融结直肠癌肝转移灶的催化剂，增加消融范围。© RSNA，2017.
Purpose To demonstrate that anti-MG1 conjugated hybrid magnetic gold nanoparticles (HNPs) act as a catalyst during photothermal ablation (PTA) of colorectal liver metastases, and thus increase ablation zones. Materials and Methods All experiments were performed with approval of the institutional animal care and use committee. Therapeutic and diagnostic multifunctional HNPs conjugated with anti-MG1 monoclonal antibodies were synthesized, and the coupling efficiency was determined. Livers of 19 Wistar rats were implanted with 5 × 106 rat colorectal liver metastasis cell line cells. The rats were divided into three groups according to injection: anti-MG1-coupled HNPs (n = 6), HNPs only (n = 6), and cells only (control group, n = 7). Voxel-wise R2 and R2* magnetic resonance (MR) imaging measurements were obtained before, immediately after, and 24 hours after injection. PTA was then performed with a fiber-coupled near-infrared (808 nm) diode laser with laser power of 0.56 W/cm2 for 3 minutes, while temperature changes were measured. Tumors were assessed for necrosis with hematoxylin-eosin staining. Organs were analyzed with inductively coupled plasma mass spectrometry to assess biodistribution. Therapeutic efficacy and tumor necrosis area were compared by using a one-way analysis of variance with post hoc analysis for statistically significant differences. Results The coupling efficiency was 22 μg/mg (55%). Significant differences were found between preinfusion and 24-hour postinfusion measurements of both T2 (repeated measures analysis of variance, P = .025) and T2* (P < .001). Significant differences also existed for T2* measurements between the anti-MG1 HNP and HNP-only groups (P = .034). Mean temperature ± standard deviation with PTA in the anti-MG1-coated HNP, HNP, and control groups was 50.2°C ± 7.8, 51°C ± 4.4, and 39.5°C ± 2.0, respectively. Inductively coupled plasma mass spectrometry revealed significant tumor targeting and splenic sequestration. Mean percentages of tumor necrosis in the anti-MG1-coated HNP, HNP, and control groups were 38% ± 29, 14% ± 17, and 7% ± 8, respectively (P = .043). Conclusion Targeted monoclonal antibody-conjugated HNPs can serve as a catalyst for photothermal ablation of colorectal liver metastases by increasing ablation zones. © RSNA, 2017.