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用于有效光动力治疗和精确三维肿瘤成像的姜黄素光稳定锰(II)配合物

Photostable Mn(II) Complex of Curcumin for Effective Photodynamic Therapy and Precise Three-Dimensional Tumor Imaging.

作者信息

Sarkar Tukki, Bera Arpan, Upadhyay Aarti, Jain Naitik, Are Varshini, Eedara Abhisheik, Prakashchandra Raval Devraj, Panneerselvam Suriya, Nanubolu Jagadeesh Babu, Andugulapati Sai Balaji, Biswas Swati, Babu Bathini Nagendra

机构信息

Department of Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.

Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India.

出版信息

ACS Appl Mater Interfaces. 2025 Mar 5;17(9):13660-13675. doi: 10.1021/acsami.4c22606. Epub 2025 Feb 21.


DOI:10.1021/acsami.4c22606
PMID:39982010
Abstract

Photoactive complexes of first-row transition metals with emission properties offer a dual approach to cancer treatment, enabling precise optical tumor detection and subsequent eradication using light. We report a photostable and photoactive mixed-ligand Mn(II) complex, , featuring a naturally occurring curcumin ligand and dipyridophenazine base. demonstrates significant visible and red light-triggered phototoxicity against cancer cells and precise tumor imaging capability . The complex exhibits an absorption band in the visible region, extending its tail into the red region, and shows excellent dark and photostability in solution. induces significant phototoxicity against HeLa (cervical), A549 (lung), and MCF-7 (breast) cancer cells (IC ≈ 1.0 μM), as well as 3D multicellular tumor spheroids, under low-energy visible (400-700 nm) and red-light (660 nm). This effect is mediated by cytotoxic singlet oxygen and proceeds via an apoptotic mechanism. Importantly, displays significantly lower toxicity toward normal HPL1D lung and HEK-293 kidney cells under similar conditions. Cellular uptake studies reveal selective accumulation of in A549 cancer cells, with mitochondrial localization, and negligible accumulation in BEAS-2B normal lung cells. Furthermore, 3D optical tumor imaging demonstrated 's selective tumor accumulation in a 4T1 breast tumor-bearing mouse model. efficacy studies using a 4T1 tumor-bearing orthotopic mouse model show that significantly reduces tumor volume and weight in a dose-dependent manner under low-energy blue laser (450 nm) irradiation, highlighting its potential as an effective photodynamic therapy (PDT) agent. Toxicological studies confirm that does not induce abnormal biochemical or hematological parameters in healthy mice. To our knowledge, this is the first report of a Mn(II) complex with curcumin and the first example of a metal complex with curcumin for combined PDT and noninvasive 3D optical tumor imaging, paving the way for nonmacrocyclic Mn-based cancer phototheranostics.

摘要

具有发光特性的第一行过渡金属光活性配合物为癌症治疗提供了一种双重方法,能够实现精确的光学肿瘤检测,并随后利用光进行根除。我们报告了一种光稳定且具有光活性的混合配体锰(II)配合物,其具有天然存在的姜黄素配体和二吡啶并菲嗪碱。该配合物对癌细胞表现出显著的可见光和红光触发的光毒性以及精确的肿瘤成像能力。该配合物在可见光区域呈现吸收带,其尾部延伸至红色区域,并且在溶液中表现出优异的暗稳定性和光稳定性。在低能量可见光(400 - 700 nm)和红光(660 nm)照射下,该配合物对HeLa(宫颈)、A549(肺)和MCF - 7(乳腺)癌细胞(IC₅₀≈1.0 μM)以及3D多细胞肿瘤球体均诱导出显著的光毒性。这种效应由细胞毒性单线态氧介导,并通过凋亡机制进行。重要的是,在类似条件下,该配合物对正常的HPL1D肺细胞和HEK - 293肾细胞的毒性显著更低。细胞摄取研究表明,该配合物在A549癌细胞中选择性积累,定位于线粒体,而在BEAS - ²B正常肺细胞中的积累可忽略不计。此外,3D光学肿瘤成像证明了该配合物在4T1荷瘤小鼠模型中在肿瘤中的选择性积累。使用4T1荷瘤原位小鼠模型进行的疗效研究表明,在低能量蓝光激光(450 nm)照射下,该配合物以剂量依赖的方式显著减小肿瘤体积和重量,突出了其作为有效光动力疗法(PDT)药物的潜力。毒理学研究证实,该配合物在健康小鼠中不会诱导异常的生化或血液学参数。据我们所知,这是关于含姜黄素的锰(II)配合物的首次报道,也是含姜黄素的金属配合物用于联合PDT和非侵入性三维光学肿瘤成像的首个实例,为基于非大环锰的癌症光诊疗学铺平了道路。

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Photostable Mn(II) Complex of Curcumin for Effective Photodynamic Therapy and Precise Three-Dimensional Tumor Imaging.

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