Red-Light Photocatalytic Activation of Pt(IV) Anticancer Prodrugs Using Methylene Blue

IF 3.9 3区化学 Q2 CHEMISTRY, PHYSICAL ChemCatChem Pub Date : 2024-11-10 DOI:10.1002/cctc.202401424

Ana C. Carrasco, Greta Bajetto, Stefano Scoditti, German E. Pieslinger, Francesco Gambino, Marco De Andrea, Emilia Sicilia, Virginia Martínez-Martínez, Valentina Dell'Oste, Luca Salassa

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Abstract

Catalysis-based approaches offer versatile strategies for activating anticancer prodrugs, potentially allowing precise control over drug release and localization within tumor tissues while reducing systemic toxicity. In this study, we explore the role of the phenothiazine dye methylene blue (MB⁺) as a photocatalyst in conjunction with biologically relevant electron donors to facilitate the red-light conversion of two Pt(IV) complexes, denoted as cis,cis,trans-[PtCl₂(NH₃)₂(O₂CCH₂CH₂COOH)₂] (1) and trans-[Pt(O₂CCH₂CH₂COOH)₂1R,2R-(DACH)(ox)] (2), into cisplatin and oxaliplatin, respectively. Combining spectroscopic techniques (NMR, UV–vis, and flash photolysis) with computational methods, we reveal that the doubly reduced MB⁺ (leucomethylene blue, LMB) triggers the reductive elimination of axial ligands in the two Pt(IV) precursors, generating the corresponding Pt(II) anticancer drugs. In vitro experiments conducted on the human cervical cancer cell line CaSki, which harbors multiple copies of the integrated HPV-16 genome, and on nontumoral cells (HaCat) demonstrate that coadministration with Pt(IV) prodrugs improves MB⁺’s antiproliferative efficacy in cancer cells, particularly under red light exposure. This enhancement could be attributed to the catalytic production of Pt(II) species within the cellular environment.

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亚甲基蓝红光光催化活化Pt（IV）抗癌前药

基于催化的方法为激活抗癌前药提供了多种策略，有可能精确控制药物在肿瘤组织内的释放和定位，同时降低全身毒性。在这项研究中，我们探索了吩噻嗪染料亚甲基蓝（MB+）作为光催化剂与生物学相关的电子供体一起促进两种Pt（IV）配合物的红光转化作用，分别为顺式，顺式，反式-[PtCl2(NH3)2(O2CCH2CH2COOH)2](1)和反式-[Pt(O2CCH2CH2COOH)21R,2R-(DACH)(ox)](2)，分别为顺铂和奥沙利铂。结合光谱技术（NMR， UV-vis和闪光光解）和计算方法，我们发现双重还原的MB+ （leucomethylene blue， LMB）触发两种Pt（IV）前体中轴向配体的还原消除，生成相应的Pt（II）抗癌药物。在人宫颈癌细胞系CaSki和非肿瘤细胞（HaCat）上进行的体外实验表明，与Pt（IV）前药共同给药可提高MB+在癌细胞中的抗增殖作用，特别是在红光照射下。CaSki细胞系含有HPV-16基因组的多个拷贝。这种增强可能归因于细胞环境中Pt（II）物种的催化生产。

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来源期刊

ChemCatChem 化学-物理化学

CiteScore

8.10

自引率

4.40%

发文量

511

审稿时长

1.3 months

期刊介绍： With an impact factor of 4.495 (2018), ChemCatChem is one of the premier journals in the field of catalysis. The journal provides primary research papers and critical secondary information on heterogeneous, homogeneous and bio- and nanocatalysis. The journal is well placed to strengthen cross-communication within between these communities. Its authors and readers come from academia, the chemical industry, and government laboratories across the world. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and is supported by the German Catalysis Society.