Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors.

中文翻译：

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工程化人类纳米铁蛋白，带有Genz-644282药物，可用于癌症治疗

胃肠道肿瘤，包括胰腺癌和大肠癌，是全球最大的公共卫生问题之一，导致全球百万人死亡。最近的研究表明，人重链铁蛋白（HFt）可以在其腔中封装不同类型的药物，并且可以在几种实体和血液肿瘤中与受体CD71结合，从而突出了铁蛋白在靶向肿瘤治疗中的潜在用途。在这里，我们描述了基于HFt的新型纳米药物The-0504的开发和表征。特别地，这种新颖的系统是一种纳米组件，其中包含HFt的工程版本，可捕获约80个分子的有效，广谱，非喜树碱拓扑异构酶I抑制剂（Genz-644282）。可以通过标准化的工业化前工艺将-0504制成具有良好冻干特性的纯净均匀配方的产品。在培养的癌细胞和胰腺癌小鼠模型中评估了初步的抗癌活性。此处报道的总体结果使The-0504成为针对表达CD-71的致命肿瘤的进一步临床前开发的候选药物。