Development and evaluation of a theranostic probe with RGD peptide introduced platinum complex to enable tumor-specific accumulation
Development and evaluation of a theranostic probe with RGD peptide introduced platinum complex to enable tumor-specific accumulation
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DOI：
10.1016/j.bmc.2022.116919
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发表时间：
2022-07-08
影响因子：
3.5
通讯作者：
Ogawa，Kazuma
中科院分区：
文献类型：
--
作者：
Echigo，Hiroaki;Mishiro，Kenji;Ogawa，Kazuma
顺铂（CDDP）已广泛用于化疗。然而，由于其肿瘤选择性低，它具有一些不利的副作用。在本研究中，我们设计、合成并评估了 Pt(IV)-[c(RGDyK)]2(9)，其中将两个 RGD 肽分子作为癌症载体分子引入到奥索铂（CDDP 的 Pt(IV) 前药）中，以增强癌症选择性。此外，我们制备并评估了 Pt(IV)-[c(RGDyK)]{[125I]c[RGDy(3-I)K]} ([125I]10)，用于核医学成像和治疗诊断学的初步步骤。在细胞活力测定中，化合物 9 抑制细胞生长，并且在生物分布研究中，[125I]10 在肿瘤组织中高度积累（1 小时：3.53 ± 0.53%ID/g）。这些结果表明，将 RGD 肽应用到奥索铂中能够实现肿瘤特异性积累，并且结合 [123/124I]10 和 9 进行诊断成像和治疗可能有助于癌症治疗诊断。
Cisplatin (CDDP) has been widely used for chemotherapy. However, it has several unfavorable side effects due to its low tumor selectivity. In this study, we designed, synthesized, and evaluated Pt(IV)-[c(RGDyK)]2(9), in which two molecules of an RGD peptide are introduced as a carrier molecule to cancer into oxoplatin, a Pt(IV) prodrug of CDDP, to enhance cancer selectivity. Furthermore, we prepared and evaluated Pt(IV)-[c(RGDyK)]{[125I]c[RGDy(3-I)K]} ([125I]10) for a preliminary step of nuclear medicine imaging and theranostics. Compound9inhibited cell growth in the cell viability assay and, [125I]10was highly accumulated in tumor tissues (1 h: 3.53 ± 0.53 %ID/g) in the biodistribution study. These results indicate that implementing RGD peptides into oxoplatin enabled tumor-specific accumulation, and combining [123/124I]10and9for diagnostic imaging and therapy could be useful for cancer theranostics.