Department of Radiology, First Affiliated Hospital of China Medical University Shenyang, 11,0001, Liaoning, China.
Department of Radiology, First Affiliated Hospital of China Medical University Shenyang, 11,0001, Liaoning, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, First Affiliated Hospital of China Medical University Shenyang, 11,0001, Liaoning, China.
J Vasc Interv Radiol. 2019 Dec;30(12):2026-2035.e2. doi: 10.1016/j.jvir.2019.04.014. Epub 2019 Oct 4.
To evaluate the effect of transarterial infusion of iRGD-modified and doxorubicin-loaded zirconia-composite nanoparticles (R-DZCNs) with lipiodol in the improvement of the distribution of doxorubicin (DOX) in liver tumors and its antitumor efficacy.
The effect of R-DZCNs was evaluated in vitro by tumor cellular uptake and cytotoxicity assays. For the in vivo study, DOX distribution and antitumor efficiency were assessed. In the DOX distribution study, VX2 tumor-bearing rabbits received transarterial infusion of lipiodol with DOX, doxorubicin-loaded zirconia-composite nanoparticles (DZCNs), or R-DZCNs, respectively. DOX distribution was assessed by immunofluorescence. In the antitumor study, tumor-bearing rabbits received transarterial infusions of lipiodol with DOX, DZCNs, R-DZCNs, or saline respectively. Tumor volume was measured using magnetic resonance imaging, and the expression of apoptosis-related factors (caspase-3, Bax, Bcl-2) was analyzed by immunohistochemistry and Western blotting.
R-DZCNs increased cellular uptake and caused stronger cytotoxicity. Compared with the DOX + lipiodol or DZCNs + lipiodol group, the R-DZCNs + lipiodol group showed more DOX fluorescence spots (2,449.15 ± 444.14 vs. 3,464.73 ± 632.75 or 5,062.25 ± 585.62, respectively; P < .001) and longer penetration distance (117.58 ± 19.36 vs 52.64 ± 8.53 or 83.37 ± 13.76 μm, respectively; P < .001). In the antitumor study, the R-DZCNs + lipiodol group showed smaller tumor volumes than the DOX + lipiodol or DZCNs + lipiodol group (1,223.87 ± 223.58 vs. 3,695.26 ± 666.25 or 2281.06 ± 457.21 mm, respectively; P = .005).The greatest extent of tumor cell apoptosis was observed in R-DZCNs + lipiodol group immunohistochemistry and Western blotting results.
Transarterial infusion of R-DZCNs with lipiodol improved the distribution of DOX and enhanced its antitumor efficacy.
评估载阿霉素的氧化锆复合纳米粒（DZCNs）与载阿霉素的 iRGD 修饰氧化锆复合纳米粒（R-DZCNs）联合碘化油经肝动脉输注治疗对提高肝癌内阿霉素（DOX）分布及抗肿瘤疗效的影响。
通过肿瘤细胞摄取和细胞毒性试验评估 R-DZCNs 的效果。在体内研究中，评估 DOX 分布和抗肿瘤效率。在 DOX 分布研究中，VX2 荷瘤兔分别经肝动脉输注载 DOX 的碘化油、载 DZCNs 的碘化油或 R-DZCNs 的碘化油。通过免疫荧光法评估 DOX 分布。在抗肿瘤研究中，荷瘤兔分别经肝动脉输注载 DOX 的碘化油、载 DZCNs 的碘化油、R-DZCNs 的碘化油或生理盐水。采用磁共振成像测量肿瘤体积，并通过免疫组化和 Western blot 分析凋亡相关因子（caspase-3、Bax、Bcl-2）的表达。
R-DZCNs 增加了细胞摄取并引起更强的细胞毒性。与 DOX+碘化油或 DZCNs+碘化油组相比，R-DZCNs+碘化油组显示出更多的 DOX 荧光点（2,449.15±444.14 比 3,464.73±632.75 或 5,062.25±585.62，P<.001）和更长的渗透距离（117.58±19.36 比 52.64±8.53 或 83.37±13.76 μm，P<.001）。在抗肿瘤研究中，与 DOX+碘化油或 DZCNs+碘化油组相比，R-DZCNs+碘化油组的肿瘤体积更小（1,223.87±223.58 比 3,695.26±666.25 或 2,281.06±457.21 mm，P=.005）。R-DZCNs+碘化油组的肿瘤细胞凋亡程度最大，免疫组化和 Western blot 结果也证实了这一点。
肝动脉输注 R-DZCNs 联合碘化油可改善 DOX 的分布，增强其抗肿瘤疗效。
