血管介入放射学引导下金纳米棒光热治疗结直肠癌肝转移
Vascular Interventional Radiology-Guided Photothermal Therapy of Colorectal Cancer Liver Metastasis with Theranostic Gold Nanorods
作者:Abdul Kareem Parchur;Gayatri Sharma;Jaidip M. Jagtap;Venkateswara Rao Gogineni;Peter S. LaViolette;Michael J. Flister;Sarah Beth White;Amit Joshi;
关键词:colorectal cancer liver metastasis,image-guided interventional therapy,laser ablation,MR contrast,X-ray contrast,gold nanorods
DOI:https://doi.org/10.1021/acsnano.8b01424
发表时间:2018年
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摘要
我们报告了亚 100 nm 光学/磁共振 (MR)/X 射线对比治疗诊断纳米粒子 (TNP),用于实体瘤的介入图像引导光热治疗 (PTT)。 TNP 由 Au@Gd2O3:Ln (Ln = Yb/Er) 组成,X 射线对比度 (486 HU; 1014 NPs/mL, 0.167 nM) 和 MR 对比度 (1.1 × 108 mM–1 S–1 在 9.4 T 场强)。尽管 TNP 在全身给药后通过增强的渗透和滞留效应沉积在肿瘤中,但递送至肿瘤的剂量通常较低;这会对 PTT 的功效产生不利影响。为了克服这一限制,我们研究了在结直肠肝转移 (CRLM) 大鼠中进行位点选择性肝脏图像引导 TNP 递送的可行性。对荷瘤大鼠的肠系膜静脉插管,通过门静脉将 TNP 注入肝脏进行位点选择性递送。将通过肝脏递送的 TNP 的摄取与全身给药进行比较。 MR 成像证实,与全身给药相比,通过肝门静脉给药可使 CRLM 肿瘤与肝脏的对比度加倍。通过在 DynaCT 图像引导下通过 JB1、3-French 导管插入携带 808 nm 光的 100 μm 光纤 3 分钟来进行光热消融。组织学分析显示,热损伤主要局限于肿瘤区域,对邻近肝组织的损伤最小。透射电子显微镜成像验证了 PTT 前后体内 TNP 核壳结构的稳定性。通过利用介入放射学方法,包含 Gd 壳涂层金纳米棒的 TNP 可以有效地用于 CRLM 的定点 PTT。
Abstract
We report sub-100 nm optical/magnetic resonance (MR)/X-ray contrast-bearing theranostic nanoparticles (TNPs) for interventional image-guided photothermal therapy (PTT) of solid tumors. TNPs were composed of Au@Gd2O3:Ln (Ln = Yb/Er) with X-ray contrast (∼486 HU; 1014 NPs/mL, 0.167 nM) and MR contrast (∼1.1 × 108 mM–1 S–1 at 9.4 T field strength). Although TNPs are deposited in tumors following systemic administration via enhanced permeation and retention effect, the delivered dose to tumors is typically low; this can adversely impact the efficacy of PTT. To overcome this limitation, we investigated the feasibility of site-selective hepatic image-guided delivery of TNPs in rats bearing colorectal liver metastasis (CRLM). The mesenteric vein of tumor-bearing rats was catheterized, and TNPs were infused into the liver by accessing the portal vein for site-selective delivery. The uptake of TNPs with hepatic delivery was compared with systemic administration. MR imaging confirmed that delivery via the hepatic portal vein can double the CRLM tumor-to-liver contrast compared with systemic administration. Photothermal ablation was performed by inserting a 100 μm fiber-optic carrying 808 nm light via a JB1, 3-French catheter for 3 min under DynaCT image guidance. Histological analysis revealed that the thermal damage was largely confined to the tumor region with minimal damage to the adjacent liver tissue. Transmission electron microscopy imaging validated the stability of core–shell structure of TNPs in vivo pre- and post-PTT. TNPs comprising Gd-shell-coated Au nanorods can be effectively employed for the site-directed PTT of CRLM by leveraging interventional radiology methods.
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