Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand.
Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand.
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DOI：
10.1038/srep22668
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发表时间：
2016-03-04
影响因子：
4.6
通讯作者：
Bryant HE
中科院分区：
文献类型：
--
作者：
Doherty RE;Sazanovich IV;McKenzie LK;Stasheuski AS;Coyle R;Baggaley E;Bottomley S;Weinstein JA;Bryant HE
使用仅在光照射时变得有毒的光敏剂的光动力疗法提供了常规癌症治疗的强有力的替代方案，这是由于其选择性靶向肿瘤材料而不影响健康组织的能力。过渡金属配合物是非常有前途的PDT剂，由于强烈的可见光吸收，但大多数是有毒的，即使没有光。本研究介绍了一种小的，光稳定的，电中性的铂基化合物，Pt（II）2，6-联吡啶-4-甲基-苯甲酸，配合物1，作为光敏剂，它的工作在可见光下。低浓度（0.1-1 μM）的新型光敏剂被相对低剂量的405 nm光（3.6 J cm−2）激活，导致宫颈癌、结直肠癌和膀胱癌细胞系的显著细胞死亡，重要的是，顺铂耐药细胞系EJ-R。配合物的光致指数为8。我们证明，复合物1诱导不可逆的DNA单链断裂照射后，氧是必不可少的光诱导的行动。光和化合物都不会导致细胞死亡。这种新药的主要优点包括非常快的积累时间（扩散控制，分钟）和光稳定性。这项研究证明了一个非常有前途的新的光动力治疗剂，并吸引了人们的注意，光稳定的金属配合物作为可行的替代传统的化疗药物，如顺铂。
Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1–1 μM) by comparatively low dose of 405 nm light (3.6 J cm−2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.