Abstract Elemental selenium generated by the photobleaching of selenomerocyanine dyes forms conjugates with serum albumin and serum lipoproteins that are toxic to leukemia and selected solid tumor cells but well tolerated by normal CD34-positive hematopoietic stem and progenitor cells. Serum albumin and lipoproteins act as Trojan horses that deliver the cytotoxic entity (elemental selenium) to tumor cells as part of a physiological process. They exploit the fact that many tumors have an increased demand for albumin and/or low-density lipoprotein. Se(0)-protein conjugates are more toxic than selenium dioxide, sodium selenite, selenomethionine, or selenocystine. They are only minimally affected by a drug resistance mechanism, and they potentiate the cytotoxic effect of ionizing radiation and several standard chemotherapeutic agents. The cytotoxic mechanism of Se(0)-protein conjugates is not yet fully understood. Currently available data are consistent with the notion that Se(0)-protein conjugates act as air oxidation catalysts that cause a rapid depletion of intracellular glutathione and induce apoptosis. Drugs modeled after our Se(0)-protein conjugates may prove useful for the local and/or systemic therapy of cancer.

中文翻译：

---

硒-部花青光敏剂光漂白产生的元素硒与对肿瘤细胞有毒的血清大分子形成结合物

摘要 硒基花青染料光漂白产生的元素硒与血清白蛋白和血清脂蛋白形成结合物，这些结合物对白血病和选定的实体瘤细胞具有毒性，但正常 CD34 阳性造血干细胞和祖细胞耐受良好。血清白蛋白和脂蛋白充当特洛伊木马，将细胞毒性实体（元素硒）作为生理过程的一部分传递给肿瘤细胞。他们利用了许多肿瘤对白蛋白和/或低密度脂蛋白的需求增加的事实。Se(0)-蛋白质结合物比二氧化硒、亚硒酸钠、硒代蛋氨酸或硒代胱氨酸毒性更大。它们受耐药机制的影响很小，并且它们增强了电离辐射和几种标准化疗药物的细胞毒性作用。Se(0)-蛋白质偶联物的细胞毒性机制尚未完全了解。目前可用的数据与 Se(0)-蛋白质偶联物作为空气氧化催化剂的观点一致，可导致细胞内谷胱甘肽快速消耗并诱导细胞凋亡。以我们的 Se(0)-蛋白质偶联物为模型的药物可能被证明可用于癌症的局部和/或全身治疗。