BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Kebin Ye,Xinlu Bao,Zhikang Song,Mingzhu Zhang,Shaohua Wei,Jishuang Zhang,Lin Zhou
Photosensitizers are central to the efficacy of photodynamic therapy (PDT) in cancer treatment. The phototoxic index (PI) defines the therapeutic window of a photosensitizer, with the clinically used Photosens® exhibiting a PI of 725. In our study, we observed that Zn(II) phthalocyanine mono-β-substituted with 4-carboxyphenoxy (ZnPc-COOH) displayed a phototoxic IC 50 in bladder cancer T24 cells at approximately 11.2 nM, yet its dark toxicity was notably high, yielding a PI of only 199. We hypothesize that the elevated dark toxicity is linked to mitochondrial localization. Rather than employing traditional side-chain substitution strategies to mitigate dark toxicity, we adopted a center metal substitution approach, synthesizing the first Al(III) phthalocyanine mono-β-substituted with 4-carboxyphenoxy photosensitizer (AlPc-COOH). Remarkably, AlPc-COOH localized to the lysosome, exhibited a phototoxic IC 50 of 1 nM, and showed a nearly 89-fold reduction in dark toxicity, achieving a PI of 223,700, which is 1000 times greater than ZnPc-COOH. In a murine orthotopic bladder cancer model, AlPc-COOH demonstrated therapeutic efficacy comparable to that of the clinically used chemotherapeutic agent mitomycin C (MMC). This study provides a crucial foundation for the design of optimized mono-substituted aluminum phthalocyanine-based photosensitizers.
研究领域:
生物学
·
医学
·
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xin-Yang Zhang,Ye Du,Yao Lu,Wen-Long Wang,Qian-Yuan Wu
Ozonation plays an important role in wastewater treatment for reuse. However, the toxicity of wastewater treated with ozone considerably increases with bromide (Br − ) concentration >100 μg/L. Nine newly identified brominated disinfection byproducts (Br-DBPs) that are highly toxic in ozonated Br − -containing wastewater were found in our recent work, including 2-bromostyrene, 1-bromo-1-phenylethylene, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, 3-bromophenylacetonitrile, 4-bromophenylacetonitrile, and 2,4,6-tribromophenol. In the present study, the formation and calculated toxicity index of the nine newly identified Br-DBPs were evaluated. The correlations between the water quality index and the formation of nine Br-DBPs were also analyzed. With the increase of ozone dosage, the concentrations of bromostyrenes, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, and 2,4,6-tribromophenyl in the ozonated samples gradually increased. With the increase of Br − concentration, the concentrations of bromostyrene, 2-bromobenzaldehyde, and 2,4,6-tribromophenol gradually increased. With the increase of NH 4 + concentration, the concentrations of bromophenylacetonitriles gradually increased. Among the nine Br-DBPs, the bromophenylacetonitriles and 2,4,6-tribromophenol contributed the most to the cytotoxicity index, 2,4,6-tribromophenol and bromostyrenes contributed the most to the genotoxicity index, and bromophenylacetonitriles and bromostyrenes contributed the most to the oxidative damage index. The dissolved organic carbon levels strongly correlated with the formation of 3-bromophenylacetonitrile and 4-bromophenylacetonitrile, and the fluorescence I–V region intensity integral was correlated with the formation of 4-bromobenzaldehyde and 2,4,6-tribromophenol. The results of the present study clarified the formation potential of the nine widely existing newly identified Br-DBPs, confirmed the high calculated toxicity indices, and are of great value for future research on Br-DBPs.
研究领域:
环境科学
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毒理学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Han Chen,Tao Lin,Xiaoshu Yan,Hang Xu
The formation of haloacetonitriles (HANs) during chlorination after sulfite/ultraviolet (UV) treatment of bromate (BrO 3 − ) in the presence of amino acids (AAs) was investigated. During sulfite/UV treatment, the primary species hydrated electrons (e aq − ) and hydrogen atom radicals (H ) dominated the reduction of BrO 3 − to bromide (Br − ), whereas the sulfite anion radicals (SO 3 − ) and H degraded AAs to produce the intermediates HN=C(CH 3 )–COOH, CH 3 –CH=NH, and CH 3 –C≡N via α‑hydrogen abstraction and NH 2 –hydrogen abstraction mechanisms. During post-chlorination, Br − was converted to HBrO/BrO-, and the HN=C(CH 3 )–COOH, CH 3 –CH=NH, and CH 3 –C≡N groups featured higher bromine utilization factor (BUF) and chlorine utilization factor (CUF) values than AAs, enhancing the formation of dibromoacetonitrile (DBAN) and dichloroacetonitrile (DCAN). The energetic feasibility of the transformation pathway, that is, HN=C(CH 3 )–COOH, CH 3 –CH=NH, and CH 3 –C ≡ N formation via hydrogen abstraction by SO 3 − and H and their further conversion to HANs, was proved by density functional theory calculations, which showed stepwise negative Gibbs free energy changes (ΔG < 0). The effects of pH and water matrices (e.g., HCO 3 − , Cl − , Fe 3+ , and natural organic matter) were comprehensively evaluated. Although 72% of BrO 3 − was removed by sulfite/UV treatment in the presence of AAs, the cytotoxicity index (CTI) and genotoxicity index (GTI) during post-chlorination increased by 213% and 125%, respectively, due to the formation of 24 CX 3 R-type disinfection by-products (DBPs), especially brominated DBPs. Accordingly, more attention should be given to the formation of brominated DBPs during post-chlorination when using sulfite/UV processes to remove BrO 3 − in the presence of AAs. As a solution, using monochloramine instead of chlorine as a disinfectant after the sulfite/UV process could significantly lower the CTI and GTI values by alleviating the formation of brominated DBPs.
研究领域:
环境科学
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水处理
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化学工程
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毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED PHYCOLOGY
·
2023
·Vol. 35
·期 5
·2219-2239
·
IF 3.3
Gan Tingting,Yin Gaofang,Zhao Nanjing,Tan Xiaoxuan,Wang Ying,Sheng Ruoyu,Ye Ziqi
Microalgal fluorescence kinetics method, as a promising technique for rapidly detecting water toxicity, still lacks a consistent response index with sensitive response characteristics to different types of toxic pollutants. In order to solve this problem, in this study, the influences of six typical toxic pollutants belonging to different types, including the heavy metal cadmium, the herbicide atrazine, organic chemical raw materials 1,4-benzoquinone and 1,4-dichlorobenzene, and the disinfection by-products chloroacetic acid and trichloroacetonitrile on the fluorescence rise kinetics (OJIP) curve of microalga Chlorella pyrenoidosa were investigated. According to the same characteristics of changes in the OJIP curves of different toxic pollutant treatments, a new response index for detecting the comprehensive toxicity of water (RI ct ) was constructed. By comparing with the maximum photochemical quantum yield of photosystem II (PSII) (F v /F m ), the potential quantum yield of PSII (F v /F o ), the performance index of PSII (PI ABS ) and the quantum yield of electron transport of PSII (φ Eo ), the feasibility and sensitivity of quantitative response of RI ct to the toxicity of each pollutant and polluted water containing multiple pollutants were verified. The results indicated that all the six toxic pollutants had the same influence on parameters F v(m-j) /F o and F v(m–o) /F o contained in the OJIP curve, and RI ct constructed based on F v(m-j) /F o and F v(m–o) /F o had a good logistic curve concentration–response relationship with each pollutant. By comparison, the response sensitivity of RI ct to all pollutants was significantly superior to F v /F m , F v /F o and φ Eo , and also had better stability in the toxicity response to each pollutant compared to PI ABS , indicating that RI ct was a suitable response index for rapidly and sensitively detecting water comprehensive toxicity based on microalgal fluorescence kinetics. This study provides an important basis for the development of rapid and sensitive detection methods for water toxicity.
研究领域:
环境科学
·
生物学
✓ 已验证
产品关联
DOI
高影响因子
DYES AND PIGMENTS
·
2025
·
IF 4.2
Xinlu Bao,Kebin Ye,Zhikang Song,Mingzhu Zhang,Shaohua Wei,Lin Zhou
Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) generated by photosensitizers under light to kill cancer cells. The phototoxic index (PI) indicates the safe therapeutic window of photosensitizers, and an ideal photosensitizer should have a high PI. Monosubstituted zinc phthalocyanine (ZnPc-COOH) exhibits excellent phototoxicity in bladder cancer cell (T24, IC 50 = 10.7 nM). However, its localization in mitochondria leads to high dark toxicity (IC 50 = 2.12 μM), resulting in a PI of less than 200. In this study, the binding ability of phthalocyanine to the cell membrane was significantly enhanced by side-chain modification with arginine. By taking advantage of the fluidity of the membrane structure, the drug was transported to the lysosome. After modification with Arg, the dark toxicity of ZnPc-COOH decreased by nearly 100 times, and the PI increased to 8979, which is 12 times that of the clinical photosensitizer Photosens®. In a mouse model of non-muscle-invasive bladder cancer (NMIBC), ZnPc-Arg demonstrated therapeutic effects comparable to those of the clinical drug mitomycin C (MMC). This study provides valuable references for the design of photosensitizers with high PI.
研究领域:
光动力疗法
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生物化学
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药物化学
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癌症生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）