Abstract:
The therapeutic advantages of some platinum complexes as major anticancer chemotherapeutic agents and of nucleoside analogue-based compounds as essential antiviral/antitumor drugs are widely recognized. Red blood cells (RBCs) offer a potential new strategy for the targeted release of therapeutic agents due to their biocompatibility, which can protect loaded drugs from inactivation in the blood, thus improving biodistribution. In this study, we evaluated the feasibility of loading model nucleobase-containing Pt(II) complexes into human RBCs that were highly stabilized by four N-donors and susceptible to further modification for possible antitumor/antiviral applications. Specifically, platinum-based nucleoside derivatives [PtII(dien)(N7-Guo)]2+, [PtII(dien)(N7-dGuo)]2+, and [PtII(dien)(N7-dGTP)] (dien = diethylenetriamine; Guo = guanosine; dGuo = 2\'-deoxy-guanosine; dGTP = 5\'-(2\'-deoxy)-guanosine-triphosphate) were investigated. These Pt(II) complexes were demonstrated to be stable species suitable for incorporation into RBCs. This result opens avenues for the possible incorporation of other metalated nucleobases analogues, with potential antitumor and/or antiviral activity, into RBCs.
摘要:
一些铂络合物作为主要的抗癌化学治疗剂和基于核苷类似物的化合物作为必需的抗病毒/抗肿瘤药物的治疗优势已被广泛认可。红细胞(RBC)由于其生物相容性,为靶向释放治疗剂提供了潜在的新策略,可以保护装载的药物免受血液中的失活,从而改善生物分布。在这项研究中,我们评估了将模型含核碱基的Pt(II)复合物加载到人类红细胞中的可行性,这些红细胞由四个N供体高度稳定,并且易于进一步修饰以用于可能的抗肿瘤/抗病毒应用。具体来说,铂类核苷衍生物[PtII(dien)(N7-Guo)]2+,[PtII(dien)(N7-dGuo)]2+,和[PtII(dien)(N7-dGTP)](dien=二亚乙基三胺;Guo=鸟苷;dGuo=2'-脱氧鸟苷;dGTP=5'-(2'-脱氧)-鸟苷-三磷酸)进行了研究。这些Pt(II)络合物被证明是适合掺入RBC中的稳定物质。该结果为可能掺入其他金属化核碱基类似物开辟了途径,具有潜在的抗肿瘤和/或抗病毒活性,进入红细胞。