Abstract Ribosome-inactivating proteins (RIPs) are potent protein toxins for cancer therapy, and they have strong ability to inhibit protein synthesis and induce cell death via inactivation of ribosomes in eukaryotic cells. However, the delivery of RIPs has been a challenging task due to their large molecular weight and lack of targeting property. Low molecular weight protamine (LMWP), a transmembrane peptide, has been proved to effectively promote transmembrane transportation, whereas the enzyme-activatable system can enhance the specificity by enhancing the tumor drug concentration through enzymatic reaction. We herein constructed a self-assembly and stimuli-responsive fusion gelonin delivery system. Gelonin, a typical RIP protein, was assembled with nickel ferrite nanoparticles by self-assembling between hexa-histidine tag (His-tagged) and nickel ions. Both in vitro and in vivo results indicated that the magnetic nanoparticle carriers and the applied linkers did not damage the pharmaceutical effect of gelonin, and the whole drug delivery system showed good biocompatibility, sensitive selectivity, and significantly enhanced cytotoxic activity. This in turn presented theranostic nanoparticles as efficient delivery vehicle for clinical use.

中文翻译：

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用于肿瘤治疗的自组装和刺激响应融合 Gelonin 递送系统

摘要 核糖体失活蛋白（RIPs）是一种有效的癌症治疗蛋白毒素，通过使真核细胞中的核糖体失活，具有很强的抑制蛋白质合成和诱导细胞死亡的能力。然而，由于 RIP 的分子量大且缺乏靶向性，其递送一直是一项具有挑战性的任务。低分子量鱼精蛋白 (LMWP) 是一种跨膜肽，已被证明可以有效促进跨膜转运，而酶激活系统可以通过酶促反应提高肿瘤药物浓度来增强特异性。我们在此构建了一个自组装和刺激响应融合gelonin 传递系统。Gelonin，一种典型的 RIP 蛋白，通过六组氨酸标签（His-tagged）和镍离子之间的自组装，与镍铁氧体纳米颗粒组装在一起。体外和体内结果均表明磁性纳米颗粒载体和应用的接头没有破坏gelonin的药效，整个给药系统表现出良好的生物相容性、灵敏的选择性和显着增强的细胞毒活性。这反过来又提出了治疗诊断纳米粒子作为临床使用的有效递送载体。