Transarterial Infusion of iRGD-Modified ZrO2 Nanoparticles with Lipiodol Improves the Tissue Distribution of Doxorubicin and Its Antitumor Efficacy |
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| Authors: | Yang Xie Xun Qi Ke Xu Xianwei Meng Xiaowei Chen Fan Wang Hongshan Zhong |
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| Institution: | 1. Department of Radiology, First Affiliated Hospital of China Medical University Shenyang, 11,0001, Liaoning, China;2. Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, First Affiliated Hospital of China Medical University Shenyang, 11,0001, Liaoning, China;3. Laboratory of Controllable Preparation and Application of Nanomaterials, Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China |
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| Abstract: | PurposeTo 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.Materials and MethodsThe 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.ResultsR-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 mm3, respectively; P = .005).The greatest extent of tumor cell apoptosis was observed in R-DZCNs + lipiodol group immunohistochemistry and Western blotting results.ConclusionsTransarterial infusion of R-DZCNs with lipiodol improved the distribution of DOX and enhanced its antitumor efficacy. |
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| Keywords: | DOX doxorubicin DZCNs doxorubicin-loaded zirconia composite nanoparticles HCC hepatocellular carcinoma IHC immunohistochemistry R-DZCNs iRGD peptide-modified and doxorubicin-loaded zirconia composite nanoparticles |
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