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一种用于结肠癌免疫治疗的、靶向叶酸受体的脂质体复合物,其可递送白细胞介素-15基因。

A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy.

作者信息

Liang Xiao, Luo Min, Wei Xia-Wei, Ma Cui-Cui, Yang Yu-Han, Shao Bin, Liu Yan-Tong, Liu Ting, Ren Jun, Liu Li, He Zhi-Yao, Wei Yu-Quan

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

出版信息

Oncotarget. 2016 Aug 9;7(32):52207-52217. doi: 10.18632/oncotarget.10537.

Abstract

Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0.001) and reduced tumor nodule formation (P < 0.001). Moreover, when compared to other lipoplex-treated mice, F-PLP/pIL15-treated mice showed higher levels of IL15 secreted in the serum (P < 0.001) and ascites (P < 0.01). These results suggested that the targeted delivery of IL15 gene might be associated with its in vivo antitumor effects, which include inducing tumor cell apoptosis, inhibiting tumor proliferation and promoting the activation of immune cells such as T cells and natural killer cells. Furthermore, hematoxylin and eosin staining of vital organs following F-PLP/pIL15 treatment showed no detectable toxicity, thus indicating that intraperitoneal administration may be a viable route of delivery. Overall, these results suggest that F-PLP/pIL15 may serve as a potential targeting preparation for colon cancer therapy.

摘要

白细胞介素-15已被认为是癌症免疫治疗中一种有前景的细胞因子,而叶酸受体α(FRα)已被证明是结肠癌治疗的一个潜在有用靶点。在此,我们开发了F-PLP/pIL15,一种靶向FRα的脂质体复合物,其负载重组白细胞介素-15质粒(pIL15),并使用CT26结肠癌小鼠模型在体内研究了其抗肿瘤作用。与对照(生理盐水)治疗相比,F-PLP/pIL15在肿瘤重量方面显著抑制了肿瘤生长(P < 0.001),并减少了肿瘤结节的形成(P < 0.001)。此外,与其他脂质体复合物处理的小鼠相比,F-PLP/pIL15处理的小鼠血清(P < 0.001)和腹水中分泌的IL15水平更高(P < 0.01)。这些结果表明,IL15基因的靶向递送可能与其体内抗肿瘤作用相关,这些作用包括诱导肿瘤细胞凋亡、抑制肿瘤增殖以及促进免疫细胞如T细胞和自然杀伤细胞的活化。此外,F-PLP/pIL15处理后重要器官的苏木精和伊红染色未显示可检测到的毒性,因此表明腹腔内给药可能是一种可行的给药途径。总体而言,这些结果表明F-PLP/pIL15可能作为结肠癌治疗的一种潜在靶向制剂。

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