Near-infrared absorbing Ru(ii) complexes act as immunoprotective photodynamic therapy (PDT) agents against aggressive melanoma.
Near-infrared absorbing Ru(ii) complexes act as immunoprotective photodynamic therapy (PDT) agents against aggressive melanoma.
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DOI：
10.1039/d0sc03875j
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发表时间：
2020-11-21
期刊：
影响因子：
8.4
通讯作者：
McFarland SA
中科院分区：
文献类型：
--
作者：
Lifshits LM;Roque Iii JA;Konda P;Monro S;Cole HD;von Dohlen D;Kim S;Deep G;Thummel RP;Cameron CG;Gujar S;McFarland SA
在过去的20年中，越来越多的证据表明，光动力疗法（PDT），一种主要被称为局部治疗的抗癌方式，有能力引起全身抗肿瘤免疫反应，从而防止肿瘤复发。对于恶性肿瘤如黑色素瘤，其中化疗和放疗无效，免疫调节PDT作为手术的辅助是有意义的。为了开发用于治疗色素性黑色素瘤的专用光敏剂（PS），探索了基于Ru（ii）三混配支架[Ru（NNN）（NN）（L）]Cln的九种新的近红外（NIR）吸收PS。化合物2、6和9对黑色素瘤细胞表现出高效力，可见EC 50值低至0.292-0.602 μM，PI高达156-360。单微摩尔的光毒性，获得了近红外线（733 nm）与PI高达71。这些前导NIR PS的共同特征是对于高单线态氧（1 O2）量子产率（69-93%）而言可接近的低能量三重态配体内（3 IL）激发态，这仅在光敏3 IL态的能量低于通常支配Ru（ii）多吡啶基光物理的最低三重态金属-配体电荷转移（3 MLCT）激发态时才可能。用2进行的PDT治疗在小鼠B16 F10黑色素瘤细胞中引起促炎反应以及免疫原性细胞死亡，并且证明对于体内施用是安全的（最大耐受剂量= 50 mg kg-1）。用B16 F10细胞接种的雌性和雄性小鼠，经2 PDT处理并用活B16 F10细胞激发，分别表现出80%和55%的肿瘤生长保护，导致存活率显著提高，风险比≤0.2。Ru（ii）光敏剂（PS）破坏侵袭性黑色素瘤细胞，引发免疫反应，导致保护免受肿瘤攻击和小鼠存活。
Mounting evidence over the past 20 years suggests that photodynamic therapy (PDT), an anticancer modality known mostly as a local treatment, has the capacity to invoke a systemic antitumor immune response, leading to protection against tumor recurrence. For aggressive cancers such as melanoma, where chemotherapy and radiotherapy are ineffective, immunomodulating PDT as an adjuvant to surgery is of interest. Towards the development of specialized photosensitizers (PSs) for treating pigmented melanomas, nine new near-infrared (NIR) absorbing PSs based on a Ru(ii) tris-heteroleptic scaffold [Ru(NNN)(NN)(L)]Cln, were explored. Compounds 2, 6, and 9 exhibited high potency toward melanoma cells, with visible EC50 values as low as 0.292–0.602 μM and PIs as high as 156–360. Single-micromolar phototoxicity was obtained with NIR-light (733 nm) with PIs up to 71. The common feature of these lead NIR PSs was an accessible low-energy triplet intraligand (3IL) excited state for high singlet oxygen (1O2) quantum yields (69–93%), which was only possible when the photosensitizing 3IL states were lower in energy than the lowest triplet metal-to-ligand charge transfer (3MLCT) excited states that typically govern Ru(ii) polypyridyl photophysics. PDT treatment with 2 elicited a pro-inflammatory response alongside immunogenic cell death in mouse B16F10 melanoma cells and proved safe for in vivo administration (maximum tolerated dose = 50 mg kg−1). Female and male mice vaccinated with B16F10 cells that were PDT-treated with 2 and challenged with live B16F10 cells exhibited 80 and 55% protection from tumor growth, respectively, leading to significantly improved survival and excellent hazard ratios of ≤0.2. Ru(ii) photosensitizers (PSs) destroy aggressive melanoma cells, triggering an immune response that leads to protection against tumor challenge and mouse survival.
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影响因子：
4.7
作者：
Budhwani M;Mazzieri R;Dolcetti R
通讯作者：
Dolcetti R
DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
10.3
作者：
Chen, Kevin G.;Leapman, Richard D.;Gottesman, Michael M.
通讯作者：
Gottesman, Michael M.
影响因子：
4.5
作者：
Azzouzi, Abdel-Rahmene;Barret, Eric;Emberton, Mark
通讯作者：
Emberton, Mark
影响因子：
3.3
作者：
Allison, Ron R.
通讯作者：
Allison, Ron R.