Toubia Isabelle, Nguyen Christophe, Diring Stéphane, Pays Marine, Mattana Elodie, Arnoux Philippe, Frochot Céline, Gary-Bobo Magali, Kobeissi Marwan, Odobel Fabrice
CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, CNRS, UMR CNRS 6230, Université de Nantes, 2, rue de la Houssinière-BP 92208, CEDEX 3, 44322 Nantes, France.
LRGP, Laboratoire Réactions et Génie des Procédés, UMR 7274 CNRS-Université de Lorraine, 1 rue Grandville, 54000 Nancy, France.
Pharmaceuticals (Basel). 2021 Apr 28;14(5):413. doi: 10.3390/ph14050413.
The combination of photodynamic therapy and chemotherapy is a promising strategy to enhance cancer therapeutic efficacy and reduce drug resistance. In this study two zinc(II) phthalocyanine-tin(IV) conjugates linked by a triethylene glycol chain were synthesized and characterized. In these complexes, the zinc(II) phthalocyanine was used as a potential photosensitizer for PDT and the tin complex was selected as cytostatic moiety. The two dyads composed of zinc(II) phthalocyanine and tin complexes exhibited high cytotoxicity, in absence of light stimulation, against MCF-7 human breast cancer cells with low LC values in the range of 0.016-0.453 µM. In addition, these complexes showed superior cytotoxicity than their mixture of equimolar component, accompanied with a higher activity towards cancer cells compared to human healthy fibroblasts. However, under irradiation of the zinc phthalocyanine unit (at 650 nm) no photodynamic activity could be detected, due to the most likely quenching of zinc(II) phthalocyanine singlet excited state by the nearby tin complex according to a photoinduced electron transfer process. This study demonstrates the potential of heterometallic anticancer chemotherapeutics composed of a zinc phthalocyanine and tin complex, and it highlights that the development of such conjugates requires that the sensitizer preserves its photophysical properties and in particular its singlet oxygen sensitization ability in the conjugate in order to combine the PDT activity with the cytotoxicity of the anticancer drug.
光动力疗法与化疗相结合是一种很有前景的策略，可提高癌症治疗效果并降低耐药性。在本研究中，合成并表征了两种由三甘醇链连接的锌（II）酞菁 - 锡（IV）共轭物。在这些配合物中，锌（II）酞菁用作光动力疗法的潜在光敏剂，锡配合物用作细胞生长抑制剂部分。由锌（II）酞菁和锡配合物组成的两种二元化合物在无光刺激的情况下对MCF - 7人乳腺癌细胞表现出高细胞毒性，低半数致死浓度（LC）值在0.016 - 0.453 μM范围内。此外，这些配合物比其等摩尔组分的混合物表现出更高的细胞毒性，与人类健康成纤维细胞相比，对癌细胞具有更高的活性。然而，在锌酞菁单元（650 nm）的照射下，未检测到光动力活性，这很可能是由于根据光诱导电子转移过程，附近的锡配合物淬灭了锌（II）酞菁单重激发态。本研究证明了由锌酞菁和锡配合物组成的异金属抗癌化疗药物的潜力，并强调此类共轭物的开发要求敏化剂在共轭物中保留其光物理性质，特别是其单线态氧敏化能力，以便将光动力疗法活性与抗癌药物的细胞毒性相结合。
