期刊
ACS NANO
卷 12, 期 7, 页码 6597-6611出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b01424
关键词
colorectal cancer liver metastasis; image-guided interventional therapy; laser ablation; MR contrast; X-ray contrast; gold nanorods
类别
资金
- NIH [R01 CA193343, R01 CA218144]
- MCW Cancer Center (WBCS)
- MCW Center for Imaging Research, Radiology
- Alliance for Healthy Wisconsin
- Rock River Cancer Research Foundation (RRCRF)
- MCW Research Affairs Committee (RAC)
- American Cancer Society [86-004-26]
- RSNA Research Scholar Grant
- Medical College of Wisconsin Cancer Center
- Dr. Nancy Sobczak Fund for Breast Cancer
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 (similar to 486 HU; 10(14) NPs/mL, 0.167 nM) and MR contrast (similar to 1.1 x 10(8) 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 mu m 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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