Optimizing Arsenic Therapy by Selectively Targeting Leukemia Cells

Arsenic, in the simple form of arsenic trioxide, is currently
marketed
for the treatment of acute promyelocytic leukemia. Due to the multifaceted
mechanisms of action of arsenic, it has also shown promise in other
types of leukemias but is hindered by its toxic effects toward normal
cells. This research has aimed to determine whether tumor-homing peptide
complexes of arsenic can be designed and developed to strategically
target specific cancers. The end goal is to achieve dose reduction
and decreased side effects of the resultant arsenic therapeutic agent.
In this article, we present the synthesis, characterization, and stability
studies of a new class of As-peptide complexes designed to target
leukemia. In vitro biological studies of the most
stable complex show 1000 times greater toxicity toward leukemia cells
over human blood cells, indicating potential for progression to in vivo studies.

以三氧化二砷（arsenic trioxide）为单一活性形式的砷制剂，目前已被批准用于急性早幼粒细胞白血病的治疗。鉴于砷的作用机制具有多效性，其在其他白血病亚型中也展现出应用前景，但因对正常细胞存在毒性作用而制约了临床拓展。本研究旨在探索能否设计并构建砷的肿瘤归巢肽（tumor-homing peptide）复合物，以实现对特定癌症的靶向递送。本研究的最终目标是降低此类砷基治疗药物的给药剂量并减轻其毒副作用。本文报道了一类新型靶向白血病的砷-肽复合物的合成、表征与稳定性研究。对其中稳定性最优的复合物开展的体外生物学实验结果显示，其对白血病细胞的毒性强度为人血细胞的1000倍，表明该复合物具备推进至体内实验研究的潜力。