Chitosan nanoparticle-based delivery of fused NKG2D-IL-21 gene suppresses colon cancer growth in mice.
Chitosan nanoparticle-based delivery of fused NKG2D-IL-21 gene suppresses colon cancer growth in mice.
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基于壳聚糖纳米颗粒的融合 NKG2D-IL-21 基因的递送可抑制小鼠结肠癌的生长
DOI：
10.2147/ijn.s128032
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发表时间：
2017
影响因子：
8
通讯作者：
Gong W
中科院分区：
文献类型：
--
作者：
Tan L;Han S;Ding S;Xiao W;Ding Y;Qian L;Wang C;Gong W
纳米颗粒可以负载外源DNA用于具有免疫刺激功能的细胞因子的潜在表达。NKG 2D识别人主要组织相容性复合物I类链相关蛋白和小鼠视黄酸早期诱导转录物-1，其作为肿瘤相关抗原。基于白细胞介素21（IL-21）的生物制剂通过淋巴细胞活化显示出抗肿瘤活性。NKG 2D-IL-21融合蛋白理论上通过NKG 2D部分识别肿瘤细胞，并通过IL-21部分激活T细胞。在本研究中，将编码NKG 2D和IL-21基因胞外结构域的双基因片段连接，然后插入pcDNA3.1（−）质粒。制备了基于壳聚糖的PcDNA3.1-dsNKG 2D-IL-21质粒纳米颗粒。用dsNKG 2D-IL-21基因纳米颗粒预转染的肿瘤细胞可以在体外激活自然杀伤（NK）和CD 8 + T细胞。在肌肉注射基因纳米颗粒的小鼠中，血清IL-21水平提高。DsNKG 2D-IL-21基因纳米粒静脉注射后约4-24 h在肿瘤组织中蓄积。dsNKG 2D-IL-21基因纳米颗粒的治疗还通过激活体内NK和T细胞来延缓肿瘤生长并延长荷瘤小鼠的寿命。因此，dsNKG 2D-IL-21基因纳米粒具有有效的抗肿瘤活性，有望用于肿瘤治疗。
Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21) have displayed antitumor activities through lymphocyte activation. The NKG2D–IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(−) plasmid. PcDNA3.1–dsNKG2D–IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D–IL-21 gene nanoparticles can activate natural killer (NK) and CD8+ T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D–IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for ~4–24 h. Treatment of dsNKG2D–IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D–IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy.