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Growth inhibition of human ovarian carcinoma by a novel AvidinOX-anchored biotinylated camptothecin derivative
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2018-09-15 , DOI: 10.1016/j.bmcl.2018.09.017
Olga Minenkova , Loredana Vesci , Rita De Santis , Daniela Santapaola , Raffaella Cincinelli , Loana Musso , Sabrina Dallavalle , Giuseppe Giannini

Oxidized form of avidin, named AvidinOX, provides stable fixation of biotinylated molecules in tissues thus representing a breakthrough in topical treatment of cancer. AvidinOX proved to be a stable receptor for radiolabeled biotin, biotinylated antibodies and cells. In order to expand applicability of the AvidinOX-based delivery platform, in the present study we investigated the possibility to hold biotinylated chemotherapeutics in AvidinOX-treated sites. A novel biotinylated gimatecan-derived camptothecin, coded ST8161AA1, was injected at suboptimal doses into human tumors xenografted in mice alone or pre-complexed to AvidinOX. Significantly higher growth inhibition was observed when the drug was anchored to AvidinOX suggesting the potential utility of this delivery modality for the local treatment of inoperable tumors.



中文翻译:

新型抗生物素蛋白锚定的生物素化喜树碱衍生物对人卵巢癌的生长抑制

亲和素的氧化形式称为AvidinOX,可在组织中稳定固定生物素化分子,因此代表了局部治疗癌症的突破。AvidinOX被证明是放射性标记生物素,生物素化抗体和细胞的稳定受体。为了扩大基于AvidinOX的递送平台的适用性,在本研究中,我们调查了在AvidinOX处理的部位中持有生物素化化学疗法的可能性。将亚生物最佳的剂量的新型生物素化的全美替康衍生的喜树碱注射入异种移植到小鼠体内或预先与AvidinOX混合的人肿瘤中,剂量不足为最佳。当该药物锚定在AvidinOX上时,观察到明显更高的生长抑制,这表明这种递送方式对无法手术的肿瘤的局部治疗具有潜在的实用性。

更新日期:2018-09-15
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