Cycloamylose-nanogel drug delivery system-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment.
Cycloamylose-nanogel drug delivery system-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment.
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DOI：
10.1111/cas.12547
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发表时间：
2014-12
期刊：
影响因子：
5.7
通讯作者：
Mazda O
中科院分区：
文献类型：
--
作者：
Fujii H;Shin-Ya M;Takeda S;Hashimoto Y;Mukai SA;Sawada S;Adachi T;Akiyoshi K;Miki T;Mazda O
RNAi使有效和特异性的基因沉默成为可能，可能为癌症的治疗提供有用的手段。然而，安全有效的药物输送系统（DDS），适合于肿瘤内的siRNA或shRNA的交付很少建立，阻碍了RNAi技术的癌症治疗的临床应用。我们已经设计了水凝胶聚合物纳米颗粒，或纳米凝胶，并显示其有效性作为一种新的DDS的各种分子。在这里，我们研究了自组装纳米凝胶的胆固醇轴承环淀粉与精胺组（CH-CA-Spe）提供血管内皮生长因子（VEGF）特异性短干扰RNA（siVEGF）到肿瘤细胞的潜力。siVEGF/纳米凝胶复合物通过内吞途径被肾细胞癌（RCC）细胞吞噬，导致VEGF的有效敲除。肿瘤内注射的复合物显着抑制小鼠肾细胞癌的新血管形成和生长。该治疗还抑制了髓源性抑制细胞的诱导，同时降低了白细胞介素-17A的产生。因此，CH-CA-Spe纳米凝胶可能是用于治疗性siRNA的肿瘤内递送的可行DDS。结果还表明，局部抑制VEGF可能对恶性肿瘤的全身免疫反应产生积极影响。
RNAi enables potent and specific gene silencing, potentially offering useful means for treatment of cancers. However, safe and efficient drug delivery systems (DDS) that are appropriate for intra-tumor delivery of siRNA or shRNA have rarely been established, hindering clinical application of RNAi technology to cancer therapy. We have devised hydrogel polymer nanoparticles, or nanogel, and shown its validity as a novel DDS for various molecules. Here we examined the potential of self-assembled nanogel of cholesterol-bearing cycloamylose with spermine group (CH-CA-Spe) to deliver vascular endothelial growth factor (VEGF)-specific short interfering RNA (siVEGF) into tumor cells. The siVEGF/nanogel complex was engulfed by renal cell carcinoma (RCC) cells through the endocytotic pathway, resulting in efficient knockdown of VEGF. Intra-tumor injections of the complex significantly suppressed neovascularization and growth of RCC in mice. The treatment also inhibited induction of myeloid-derived suppressor cells, while it decreased interleukin-17A production. Therefore, the CH-CA-Spe nanogel may be a feasible DDS for intra-tumor delivery of therapeutic siRNA. The results also suggest that local suppression of VEGF may have a positive impact on systemic immune responses against malignancies.
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影响因子：
11.2
作者：
Shrimali RK;Yu Z;Theoret MR;Chinnasamy D;Restifo NP;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
2.9
作者：
Nakamura I;Shibata M;Gonda K;Yazawa T;Shimura T;Anazawa T;Suzuki S;Sakurai K;Koyama Y;Ohto H;Tomita R;Gotoh M;Takenoshita S
通讯作者：
Takenoshita S
影响因子：
64.5
作者：
Zamore, PD;Tuschl, T;Bartel, DP
通讯作者：
Bartel, DP
DOI：
10.1186/bcr2345
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Das Roy L;Pathangey LB;Tinder TL;Schettini JL;Gruber HE;Mukherjee P
通讯作者：
Mukherjee P
影响因子：
11.5
作者：
Verheul, Henk M. W.;Hammers, Hans;Pili, Roberto
通讯作者：
Pili, Roberto