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
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医学
·
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Yihua Yin,Mengdan Yang,Jing Xi,Weiquan Cai,Ying Yi,Guanghua He,Yue Dai,Ting Zhou,Mengqing Jiang
To improve in vitro photostability and enhance insecticidal activity, a novel esterase/glutathione (GSH) responsive photoactivated nano-pesticide delivery system was synthesized by conjugation of photoactivated pesticide phloxine B(PB) to sodium alginate (SA) via esterase/GSH sensitive phenolic ester bond followed by ultrasonic dispersion. The system was stable in PBS (pH 7.4) and could protect effectively the conjugated PB from in vitro photodegradation because of aggregation-caused quenching effect, whose maximum photodegradation rate did not exceed 10 % after 270 min illumination. However, upon exposure to esterase-6 or GSH stimulus, high photoactivity was observed due to the destruction of the system and accompanied by PB release. The combined stimulation could trigger more PB release than any single stimulus and thus resulting in a higher photoactivity. Compared with free PB, The system showed a higher phototoxicity on Sf9 insect cells and the in vitro light exposure had little influence on the phototoxicity.
研究领域:
生物化学
·
农药科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2017
·
IF 4.208
Jingjing Du,Yuyan Zhang,Lina Liu,Mingxiang Qv,Yanna Lv,Yifei Yin,Yinfei Zhou,Minghui Cui,Yanfeng Zhu,Hongzhong Zhang
ZnO nanoparticles is one of the most used materials in a wide range including antibacterial coating, electronic device, and personal care products. With the development of nanotechnology, ecotoxicology of ZnO nanoparticles has been received increasing attention. To assess the phototoxicity of ZnO nanoparticles in aquatic ecosystem , microcosm experiments were conducted on Populus nigra L. leaf litter decomposition under combined effect of ZnO nanoparticles and visible light radiation . Litter decomposition rate, pH value, extracellular enzyme activity , as well as the relative contributions of fungal community to litter decomposition were studied. Results showed that long-term exposure to ZnO nanoparticles and visible light led to a significant decrease in litter decomposition rate (0.26 m −1 vs 0.45 m -1 ), and visible light would increase the inhibitory effect (0.24 m -1 ), which caused significant decrease in pH value of litter cultures, fungal sporulation rate, as well as most extracellular enzyme activities. The phototoxicity of ZnO nanoparticles also showed impacts on fungal community composition, especially on the genus of Varicosporium , whose abundance was significantly and positively related to decomposition rate. In conclusion, our study provides the evidence for negatively effects of ZnO NPs photocatalysis on ecological process of litter decomposition and highlights the contribution of visible light radiation to nanoparticles toxicity in freshwater ecosystems .
研究领域:
生态学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2018
·
IF 3.265
Ying Tang,Rui Cai,Ding Cao,Xue Kong,Yongbo Lu
This study identifies the phototoxic potential of commercial titanium dioxide nanoparticles (TiO 2 NPs) used in sunscreens and consumer products by employing a tiered testing approach comprising physicochemical, in vitro and ex vivo tests. Our results revealed that all the test samples of TiO 2 NPs, varied in surface coating, crystallinity and primary particle size, produced hydroxyl radicals upon UVA photoexcitation as determined by electron spin resonance (ESR) spectroscopy. Their phototoxic potentials were assessed first by combining the validated 3T3 neutral red uptake phototoxicity test and red blood cell phototoxicity test and subsequently in ex vivo models of chick chorioallantoic membrane (CAM) and reconstructed human 3D skin model (H3D). Crystalline structure and particle size of TiO 2 NPs were found to exert a major influence on the photocatalytic activity and the associated phototoxic effects. Besides, a medium-sized sample with silica/alumina also exhibited high phototoxic potency with no obvious relevance to the enhanced hydroxyl radicals and lipidperoxidation. This effect might be taken place through the interaction of harmful metal ions released from the oxide coating. However, no phototoxicity was observed on a H3D skin model probably due to the lack of efficient percutaneous absorption of TiO 2 NPs. This study demonstrates the efficacy of a tiered testing strategy for identifying phototoxic hazards of TiO 2 NPs and suggests the need for a comprehensive assessment that takes account of the effects of different coating materials and potential interactions between multiple mechanisms.
研究领域:
毒理学
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材料科学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xiangmei Xiang,Juanjuan Zhou,Shaochen Lin,Nan Zhang,Gulizhabaier Abulipizi,Guikui Chen,Zhanjun Li
Microplastics (MPs) can adsorb and influence the toxicity of traditional pollutants significantly. Although the complex toxicity of MPs and molecular pollutants were frequently reported, rare work has been done on the influence of MPs on the phototoxicity of photosensitive pollutants under light illumination condition. Herein, polystyrene microplastics (PS) (~1 μm in diameter, 5.0 mg/L) was used as a model MP to investigate its influence on the phototoxicity of a soluble blue dye, methylene blue (MB) using Daphnia magna as a model organism. The results indicate that PS could adsorb MB effectively and quickly, thus led to concentrated MB on PS/water interface. D. magna ingested MB-adsorbed PS very quickly within tens of minutes. Although MB or PS alone led to negligible lethal phototoxicity to D. magna , PS significantly enhanced the lethal phototoxicity of MB (0.25 mg/L) to D. magna after light illumination (10 h) with the survival rate decreased by 63.3 % compared with the control in the dark. Further, the phototoxicity of MB was found positively consistent with PS concentration from 0.50 mg/L to 7.50 mg/L. The singlet oxygen fluorescence assay indicates that the presence of PS did not increase the total amount of singlet oxygen in the aquatic environment but increased the local concentration in the gut area via non-selective ingestion of D. magna . High level singlet oxygen generated in the gut might possibly be the main reason that led to the massive death of D. magna . Surface adsorption of photosensitive pollutants may transform inert MPs into persistent solid sources of singlet oxygen production and become a new potential lethal threat to aquatic small organisms and ecological equilibrium. This kind of MPs and light dual drive phototoxicity of photosensitive pollutants needs to paid more attention in understanding the uncertain ecological risk of MPs.
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Xue-Wen Liu,Liang Ma,Geng-Jun He,Xia Hu,Yuan-Dao Chen,Song-Bai Zhang
Photodynamic therapy (PDT) has been proven to be an important and effective therapy method with good spatial and temporal accuracy in clinical cancer treatment. Among many PDT candidates, Ru(II)-based compounds have received more attention due to their excellent photochemical and photophysical properties, high singlet oxygen ( 1 O 2 ) photogeneration, and DNA affinities. In this study, three ruthenium(II) complexes (RC1, RC2, RC3) have been designed by varying the aromatic plane area of the main ligand to adjust their 1 O 2 photogeneration, DNA affinities, DNA photodamage, and photocytoxicity. All complexes display no cytotoxicity in the dark against Hela, A549, HepG2, and BEL-7402 cells. RC1 displays no photocytotoxicity against all tumor cells. RC2 and RC3 showed high photocytotoxicity against BEL-7402 cells. The cellular uptake, cell migration, colonies assay, apoptosis analysis, and cell cycle analysis of RC2 and RC3 confirmed that the ruthenium(II) complexes might effectively enter the cancer cells, and lead to BEL-7402 cells apoptosis through DNA damage pathway. DNA photocleavage, DNA binding, and 1 O 2 measurement experiments demonstrated the DNA damage caused by RC2 and RC3 under light, compared to RC1, might be due to their high DNA affinities, large 1 O 2 quantum yields, and large lipophilicity by varying the aromatic plane area of the main ligand. Time dependent density functional theory (TDDFT) calculated results further show that two complexes exhibit the photocytotoxicity possibly via type II photoreaction mechanism because of the larger Δ S-T than O 2 and strong SOC between S n and T m . Hence, rational design of ruthenium(II) complexes by increasing DNA affinities, 1 O 2 quantum yields and lipophilicity can be regarded as an effective approach for enhanced photodynamic therapy (PDT).
研究领域:
生物化学
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肿瘤学
·
药理学
✓ 已验证
DOI
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Xiaoxi Zhao,Qinjie Zhong,Naibijiang Abudouaini,Yan Zhao,Jibin Zhang,Guozhu Tan,Guifeng Miao,Xiaowu Wang,Jianqiang Liu,Ying Pan,Xiaorui Wang
Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment, but its clinical application is constrained by unexpected phototoxicity arising from nonspecific photosensitizer activation and their “always-on” nature. Herein, we developed a switchable nanophotosensitizer, poly(cation−π) nanoparticles (NP), which achieves supramolecular assembly through cation−π interactions. By coupling choline cationic moieties with aromatic photosensitizers (ZnPc), the polymer facilitates self-assembly driven by cation−π interactions for NP engineering. Surprisingly, the photoactivity of ZnPc was completely quenched upon complexation via cation−π interactions, thereby significantly avoiding skin phototoxicity. Upon targeting tumor cells, NP undergoes a GSH-responsive degradation process that weakens cation−π interactions, leading to spontaneous restoration of photoactivity and amplifying tumor immunogenic pyroptosis. In vivo studies demonstrated that NP achieved a high tumor inhibition rate of 84% while effectively avoiding skin phototoxicity. This work provides a novel perspective for enhancing the safety and efficacy of PDT-based tumor treatment.
研究领域:
生物医学工程
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肿瘤学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2018
·
IF 6.14
Hengchang Ma,Yucheng Ma,Lei Lei,Weidong Yin,Yuan Yang,Tao Wang,Pei Yin,Ziqiang Lei,Manyi Yang,Yanfang Qin,Shaoxiong Zhang
The newly emerged pathogenic bacteria leads to the bactericides generations one by one, which is definitely a long-term and costly process. For the small organic molecule used as antibacterial materials, photostability, biomembrane penetrating ability, and long-term antibacterial ability still are questionable. In this work, we synthesized the multiple-cation-charged aggregation-induced emission (AIE)-active polymer 1,2-diphenyl-1,2-bis(4-(pyridin-4-yl)phenyl) ethane–1,8-dibromooctane (DBPE-DBO). Due to the incorporating the dark toxicity from positively charged polymers, and the phototoxicity from generation of singlet oxygen, as well as AIE-active fluorescence performance, DBPE-DBO could be employed as an efficient bacteria targeting, imaging, and killing materials. Interestingly, DBPE-DBO was less toxic to the normal mammalian cells, which leads us to verify that DBPE-DBO could be used as a very cell-membrane permeable nucleus imaging probes. Thus, our research results may provide a new concept for the designing advanced biomaterials with versatile antibacterial properties and cell imaging ability.
研究领域:
生物材料学
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微生物学
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医学影像学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2021
·
IF 3.739
Jiaxing He,Mingyue Liu,Lingfeng Yin,Ziqi Deng,Junhong Pang,Haoxian He,Li Dang,Ming-De Li
Carprofen (CP), one kind of a nonsteroidal anti-inflammatory drug, exhibits phototoxic side effects in physiology, while its phototoxic mechanism is ambiguous. To uncover CP’s photophysical and photochemical reaction processes, femtosecond to nanosecond transient absorption spectroscopies were employed to directly detect excited states and transient intermediates of CP upon UV irradiation in pure acetonitrile (MeCN), MeCN/water 1:1, and acid/alkaline buffer solutions. The transient absorption data together with DFT calculations were integrated to elucidate mechanisms for photochemical reactions of CP in different solutions. The associated photophysical and photochemical reaction pathways are dependent on various solution environments. In a pure MeCN solvent, CP is excited to a singlet state (S1) and rapidly interacts with the solvent to proceed solvent rearrangement (SR). It then undergoes vibrational cooling (VC) and proceeds intersystem crossing (ISC) to produce the lowest triplet state (3CP). 3CP finally decays to the ground state. While in a MeCN/water 1:1 solution, deprotonated S1 of CP experiences SR and VC processes, and then it is promoted to a deprotonated triplet state (3CP–). 3CP– undergoes the parallel reactions: dechlorination to a phenyl radical (2CP–) and decarboxylation to a T1 anion (3CP–(de-CO2)). Finally, both intermediates produce the radical anion species 2CP–(de-CO2). In a pH = 7.4 (MeCN/PBS 1:1) solution, 3CP– can be converted into 2CP–(de-CO2) more quickly. Interestingly, we found that the dechlorination step can be promoted in an alkaline solution. Phenyl and chlorine radicals produced in an aqueous solution may be the root cause of the drug’s harmful side effects on the human body. This may be useful to guide the design of related CP drugs with minimal phototoxicity in the pharmaceutical process.
研究领域:
药理学
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光化学
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理论化学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 15
·3062-3071
·
IF 4.726
Lei Xu,Lichao Liu,Feng Liu,Wen Li,Ruobin Chen,Yun Gao,Weian Zhang
OEGylation of porphyrins via a disulfide linkage to form a novel class of dendritic porphyrin photosensitizers (PSs) is presented. These amphiphilic PSs possess precise molecular structures which could self-assemble into spherical aggregates in aqueous solutions. Their thermoresponsiveness was investigated using UV-Vis spectroscopy, and their reduction responsive properties were inspected using dynamic light scattering and TEM measurements. Moreover, the uptake of porphyrin-containing dendritic micelles by cells and release of reduction-sensitive PSs were investigated using flow cytometry and confocal laser scanning microscopy. The results showed that the cellular uptake of dendritic micelles was more than that of free porphyrin and the uptake process was time-dependent. Additionally, the phototoxicity of these dendritic PS micelles was investigated by MTT assay. It was found that dendritic micelles exhibited efficient phototoxicity to cancer cells while the free porphyrin had nearly no toxicity under light irradiation. All results indicate that these dendritic PSs are promising for photodynamic therapy.
研究领域:
药理学
·
生物化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Zheng Liu,Zhimin Tang,Ying Yin,Miaojian Wan,Jiezhao Zhan,Li Ren
Antitumor photodynamic therapy (PDT) faces huge challenges as selectivity and phototoxic damage, requiring delivery photosensitizers (PSs) to specifically accumulate in tumors even in organelle, and avoid the phototoxic damage during delivery. Herein, a microneedle patch (AIE-mito-TPP@MN) containing mitochondria- and lysosomes- dual targeting prodrug-like PSs (AIE-mito-TPP/AlPcSNa 4 ) that is self-assembled by mitochondria-targeted aggregation-induced-emission molecule (AIE-mito-TPP) and lysosome-targeted aluminum phthalocyanine tetrasulfonate (AlPcSNa 4 ), is developed to achieve cancer-cell-organelle-specific targeting delivery for precise PDT with high selectivity and low phototoxic damage. AIE-mito-TPP/AlPcSNa 4 displays prodrug-like activity via the regulated photoactivity to reduce the phototoxic damage caused by the “always on” PSs. Meanwhile, AIE-mito-TPP/AlPcSNa 4 @MN can insert into the epidermis to achieve rapid AIE-mito-TPP/AlPcSNa 4 delivery in tumor lesion, and enhance selective accumulation in tumor cells. The higher lysosomal acidity in tumor cells facilitates AIE-mito-TPP/AlPcSNa 4 disassembly and promotes targeting. Under light irradiation, AIE-mito-TPP/AlPcSNa 4 @MN impairs mitochondrial and lysosomal function to induce deeper tumor cells apoptosis at a low dose (≈6 µg), presenting greater therapeutic efficacy than AIE-mito-TPP@MN, AlPcSNa 4 @MN, or intravenous injection. Moreover, AIE-mito-TPP/AlPcSNa 4 @MN presents good biocompatibility as lower accumulation and targeting in normal cells, as well as the regulated photoactivity of prodrug-like PSs. Therefore, the dual organelle-targeting microneedle possesses great potential for precise PDT with high selectivity.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2023
·
IF 4.4
Peiyao Wang,Silan Bai,Chen Chen,Yongtao You,Junhui Xiao,Xinrong Guo,Lishi Wang
Rose Bengal (RB) is used as a sensitizer in ambient water due to its property of catalyzing the production of singlet oxygen ( 1 O 2 ). However, this property also brings phototoxicity and carcinogenicity. The NaYF 4 :3%Er@NaYF 4 core-shell upconversion nanoparticles (UCNPs) with higher upconversion efficiency was synthesized to detect RB in ambient water. Due to fluorescence resonance energy transfer (FRET) between RB and UCNPs, the upconversion fluorescence at 538 nm emitted by UCNPs was quenched by the RB, while the emission at 566 nm of RB raised. In the best conditions, the ratiometric emission intensity F 566 /F 538 was positively proportional to RB concentration and the linear range was 0.04–15.0 μg·mL −1 (R 2 = 0.996). The detection limit (S/N = 3) of RB was 2.46 ng·mL −1 . The recoveries ranged from 99.0% to 105.6% (relative standard deviation 0.97–3.24%, n = 3) in tap water and 100.3%–104.9% (relative standard deviation 0.66–1.94%, n = 3) in lake water. This proposed method exhibits lower detection limit and larger linear, which possesses practical application value to the detection of RB in water.
研究领域:
环境科学
·
分析化学
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）