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糖缀合金属配合物作为癌症诊断和治疗剂。

Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents.

机构信息

Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 33, 56126, Pisa, Italy.

Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 13, 56124, Pisa, Italy.

出版信息

ChemMedChem. 2021 Jan 8;16(1):30-64. doi: 10.1002/cmdc.202000456. Epub 2020 Sep 3.

DOI:10.1002/cmdc.202000456
PMID:32735702
Abstract

The possibility of selectively delivering metal complexes to a defined cohort of cells on the basis of their metabolic features is a highly challenging goal, which may be extremely useful for a series of purposes, including diagnosis and therapy of pathological states, such as cancer. Tumor cells display augmented requests for carbohydrates and, in particular, for glucose in order to sustain their high proliferation rate, which causes an increased glycolytic process (Warburg effect). Since several metal complexes display diagnostic and/or therapeutic properties, their conjugation to carbohydrate portions often induce their preferential accumulation in cancer cells, similarly to what is observed with fluorodeoxyglucose (FDG). In this review we have considered the latest developments of glycoconjugates containing metal complexes in their structures. These compounds are classified as diagnostic or therapeutic agents and are further systematically discussed on the basis of the metal atom they contain. Several diagnostic techniques are possible with these probes, since, depending on the metal species included in their structures, they may be employed in nuclear medicine (PET, SPECT), magnetic resonance imaging, luminescence and phosphorescence. At the same time, the lack of selective cytotoxicity displayed by several metal-based chemotherapeutic agents, may also be solved by the conjugation of these agents to carbohydrate portions. Overall, data so far available reveal the great potential of this chemical class in the early detection and in the cure of severe neoplastic diseases, which still needs to be fully explored in the clinic.

摘要

基于代谢特征将金属配合物选择性递送至特定细胞群体的可能性是一个极具挑战性的目标,这对于一系列目的可能非常有用,包括诊断和治疗病理状态,如癌症。肿瘤细胞对碳水化合物的需求增加,特别是对葡萄糖的需求,以维持其高增殖率,这导致糖酵解过程增加(Warburg 效应)。由于几种金属配合物具有诊断和/或治疗特性,它们与碳水化合物部分的结合通常会诱导它们优先在癌细胞中积累,类似于氟脱氧葡萄糖(FDG)的观察结果。在这篇综述中,我们考虑了含有金属配合物的糖缀合物的最新发展。这些化合物被归类为诊断或治疗剂,并根据它们所含的金属原子进行系统讨论。这些探针可用于多种诊断技术,因为根据其结构中包含的金属种类,它们可用于核医学(PET、SPECT)、磁共振成像、发光和磷光。同时,由于缺乏几种基于金属的化学治疗剂的选择性细胞毒性,也可以通过将这些试剂与碳水化合物部分结合来解决。总的来说,迄今为止可用的数据显示了此类化合物在早期检测和治疗严重肿瘤疾病方面的巨大潜力,这在临床上仍需要进一步探索。

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