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学者姓名：李兴淑
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Abstract ：
Cancer still threats human health rigorously. Most current options of photosensitizers (PSs) are plagued with "always on", accounting for limited signal-to-noise ratio in the lesions and undesired side effects in normal tissues. Inspired by the redox imbalance of tumor microenvironment, redox-activated PSs (RA-PSs) are coming to frontiers that enhance diagnosis accuracy and treatment efficiency. Herein, the progress of PSs-based therapy is outlined. Furthermore, the design strategies of RA-PSs are discussed, including potential mechanism and linkage to obtain on -demand switchable optical signals. Moreover, versatile RA-PSs for real-time visualization and therapy are highlighted. Finally, future prospects and challenges are spotlighted.
Keyword ：
Activatable photosensitizer Activatable photosensitizer Cancer therapy Cancer therapy Precise tumor imaging Precise tumor imaging Redox imbalance Redox imbalance
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| GB/T 7714 | Fu, Shuwen , Chen, Zixuan , Li, Li et al. Redox-activated photosensitizers for visualizing precise diagnosis and potentiating cancer therapy [J]. | COORDINATION CHEMISTRY REVIEWS , 2024 , 507 . |
| MLA | Fu, Shuwen et al. "Redox-activated photosensitizers for visualizing precise diagnosis and potentiating cancer therapy" . | COORDINATION CHEMISTRY REVIEWS 507 (2024) . |
| APA | Fu, Shuwen , Chen, Zixuan , Li, Li , Wu, Yinwei , Liao, Yalan , Li, Xingshu . Redox-activated photosensitizers for visualizing precise diagnosis and potentiating cancer therapy . | COORDINATION CHEMISTRY REVIEWS , 2024 , 507 . |
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Abstract ：
Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light-harvesting ability not only amplifies superoxide radical (O2•-) production but also promotes heat generation upon near-infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced. © 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.
Keyword ：
Förster resonance energy transfer Förster resonance energy transfer nanostructure nanostructure photodynamic therapy photodynamic therapy renal clearable renal clearable type I photoreaction type I photoreaction
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| GB/T 7714 | Zhao, Y.-Y. , Zhang, X. , Xu, Y. et al. A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics [J]. | Angewandte Chemie - International Edition , 2024 . |
| MLA | Zhao, Y.-Y. et al. "A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics" . | Angewandte Chemie - International Edition (2024) . |
| APA | Zhao, Y.-Y. , Zhang, X. , Xu, Y. , Chen, Z. , Hwang, B. , Kim, H. et al. A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics . | Angewandte Chemie - International Edition , 2024 . |
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It remains a challenge to develop a single-component organic photosensitizer that efficiently produces hydroxyl radicals ((OH)-O-center dot) without oxygen involvement, especially while maintaining tumor-targeting capability. Herein, we propose an intelligent molecular design strategy whereby a tumor-targeted phthalocyanine is initially (OH)-O-center dot-free and can be activated by overexpressed beta-nicotinamide adenine dinucleotide sodium salt hydrate (NAD(P)H) in hypoxic tumors to efficiently produce (OH)-O-center dot under light irradiation. Furthermore, the oligomer models based on the phthalocyanine molecules were constructed by a supramolecular regulation strategy, which were in an intermediate state between monomer and nanoaggregate, to achieve enhanced (OH)-O-center dot generation. The level of NAD(P)H in cancer cells can be exhausted through two pathways, including spontaneous redox and the photocatalytic redox of phthalocyanines. As a result, the in vivo and in vitro assays illustrated that the oligomeric phthalocyanine containing N-O units (OligPcNOB) can specifically target cancer cells and tumor tissue with overexpressing biotin receptors. OligPcNOB exhibited significant photocytotoxicity even in an extremely low oxygen environment and successfully inhibited tumor progression. An oligomer model based on an activatable photosensitizer was constructed using an intelligent molecular design and supramolecular regulation strategy and demonstrated enhanced (OH)-O-center dot generation compared to the model of monomer and nanoaggregate.
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| GB/T 7714 | Li, Li , Liao, Yalan , Fu, Shuwen et al. Efficient hydroxyl radical generation of an activatable phthalocyanine photosensitizer: oligomer higher than monomer and nanoaggregate [J]. | CHEMICAL SCIENCE , 2024 , 15 (28) : 10980-10988 . |
| MLA | Li, Li et al. "Efficient hydroxyl radical generation of an activatable phthalocyanine photosensitizer: oligomer higher than monomer and nanoaggregate" . | CHEMICAL SCIENCE 15 . 28 (2024) : 10980-10988 . |
| APA | Li, Li , Liao, Yalan , Fu, Shuwen , Chen, Zixuan , Zhao, Tinghe , Fang, Luyue et al. Efficient hydroxyl radical generation of an activatable phthalocyanine photosensitizer: oligomer higher than monomer and nanoaggregate . | CHEMICAL SCIENCE , 2024 , 15 (28) , 10980-10988 . |
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Phototherapeutic nanoplatforms that combine photodynamic therapy (PDT) and photothermal therapy (PTT) with the guidance of photoacoustic (PA) imaging are an effective strategy for the treatment of tumors, but establishing a universal method for this strategy has been challenging. In this study, we present a supramolecular assembly strategy based on Forster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent (PcDA) via the anion and cation supramolecular interaction between two water-soluble phthalocyanine ramifications, PcD and PcA. This approach promotes the absorption of energy, thus enhancing the generation of reactive oxygen species (ROS) and heat by PcDA, improving its therapeutic efficacy, and overcoming the low photon utilization efficiency of conventional PSs. Notably, after the intravenous injection of PcDA, neoplastic sites could be clearly visualized using PA imaging, with a PA signal-to-liver ratio as high as 11.9. Due to these unique features, PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation. This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging. A nanostructured supramolecular phototherapeutic agent (PcDA) was developed based on the Forster resonance energy transfer mechanism. PcDA can enable the visualization of a tumor with a photoacoustic signal-to-liver ratio as high as 11.9, and 95% of tumor growth is suppressed through photodynamic and photothermal synergistic therapy at a PcDA dose of 0.8 nmol g-1 and a light dose of 300 J cm-2. image
Keyword ：
Forster resonance energy transfer Forster resonance energy transfer photoacoustic imaging photoacoustic imaging photodynamic therapy photodynamic therapy photothermal therapy photothermal therapy supramolecular assembly supramolecular assembly
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| GB/T 7714 | Zhao, Yuan-Yuan , Zhang, Xiaojun , Chen, Zixuan et al. Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging [J]. | AGGREGATE , 2024 . |
| MLA | Zhao, Yuan-Yuan et al. "Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging" . | AGGREGATE (2024) . |
| APA | Zhao, Yuan-Yuan , Zhang, Xiaojun , Chen, Zixuan , Xu, Yihui , Kim, Heejeong , Jeong, Hyunsun et al. Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging . | AGGREGATE , 2024 . |
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Abstract ：
Phthalocyanines (Pcs) are considered promising in cancer phototherapy. However, their maximum absorption wavelengths are only around 700 nm, which cannot allow deep tissue penetration and leads to poor therapeutic efficacy. To expand their clinical application, significantly shifting their absorption to longer wavelengths is urgently required. Dye J-aggregates exhibit a redshifted absorption relative to its monomer. However, Pc J-aggregates with enormous-redshifted and intense absorption is rarely reported, and little is known about the relationships between Pc structure and J-aggregation. Herein, such Pc J-aggregates are ingeniously conceived. With a yeast β-D-glucan-ursodeoxycholic acid conjugate as a potential tumor-associated macrophages (TAMs)-targeting carrier and 1-(4-carboxyethylphenoxy) zinc (II) phthalocyanine (Pc1) as a model, Pc1 J-aggregate nanoparticle (NanoPc1) is obtained via ultrasonication-aided emulsification-solvent evaporation technique. NanoPc1 displays strong absorption at 830 nm, with a 156 nm redshift. Further investigation on another twenty-four Pcs demonstrates that unsubstituted zinc (II) or magnesium (II) Pc and hydrophobic mono-substituted zinc (II) or magnesium (II) Pcs with mono-substituted phenoxy or phenylthio or naphthoxy as a substituent can readily form desired Pc J-aggregates with significant redshifts (140–165 nm). The other Pcs fail to form expected J-aggregates probably due to absence of central metals, steric hindrance on central metals (atoms), forming axial coordination on central metals, disorder tendency during self-assembly or hydrophilicity. The theoretical calculation indicates that Pc1 in its J-aggregates exhibits a spiral-like arrangement, and the reduction in the energy gap between HOMO and LUMO and variation of intermolecular π-π interaction caused by J-aggregate formation are responsible for the huge redshift. Additionally, using NanoPc1 as an exemplar, such Pc J-aggregate nanoparticles are substantiated to afford TAMs-targeted and efficient tri-modal imaging and photothermal therapy in a H22 mouse model. © 2024 Elsevier B.V.
Keyword ：
J-aggregate J-aggregate Large redshift Large redshift Multimodal phototheranostics Multimodal phototheranostics Phthalocyanine Phthalocyanine Yeast glucan Yeast glucan
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| GB/T 7714 | Tang, F. , Yu, H. , Huang, Y. et al. Phthalocyanine J-aggregate nanoparticles with enormous-redshifted and intense absorption: Potential structure-J-aggregation relationships and application in tumor-associated macrophages-targeted phototheranostics [J]. | Chemical Engineering Journal , 2024 , 496 . |
| MLA | Tang, F. et al. "Phthalocyanine J-aggregate nanoparticles with enormous-redshifted and intense absorption: Potential structure-J-aggregation relationships and application in tumor-associated macrophages-targeted phototheranostics" . | Chemical Engineering Journal 496 (2024) . |
| APA | Tang, F. , Yu, H. , Huang, Y. , Zhao, X. , Chen, Z. , Ma, H. et al. Phthalocyanine J-aggregate nanoparticles with enormous-redshifted and intense absorption: Potential structure-J-aggregation relationships and application in tumor-associated macrophages-targeted phototheranostics . | Chemical Engineering Journal , 2024 , 496 . |
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With a view to developing highly efficient photosensitizers for photodynamic therapy, herein, we prepared a series of tetra-substituted zinc(II) phthalocyanine analogues (ZPOP, ZPSP, ZPNP, and ZPNPM) modified with O-, S-, and N-bridging substituents, respectively. Compared to O- and S-bridging analogues, the N-bridging phthalocyanines showed eminent red-shifted Q band absorption (750-780 nm) and excellent reactive oxygen species (ROS) generation ability (Phi Delta = 0.90-0.97), due to the HOMO destabilization, as well as the smaller Delta EST. To improve the hydrophility and biocompatibility, we further prepared two N-bridging zinc(II) phthalocyanines (ZPN1 and ZPN2) modified with morpholine and N,N-dimethylamine moieties, respectively, along with their quaternized counterparts (QZPN1 and QZPN2). These compounds exhibited NIR-absorbing Q bands at 774-777 nm and efficient ROS generation ability in aqueous solutions, especially formulated with 1 % Cremophor EL (Cel). In vitro studies indicated that ZPN2 exhibited the highest photodynamic activity against HepG2 cells (IC50 = 0.44 +/- 0.02 mu M), because of superior cellular uptake and moderate ROS generation ability. Moreover, ZPN2 could selectively accumulate and retain in tumor tissue of H22 tumor-bearing mice. The work presents a new strategy for the development of NIR-absorbing photosensitizers.
Keyword ：
N -bridging phthalocyanine N -bridging phthalocyanine Near-infrared Near-infrared Photodynamic therapy Photodynamic therapy Reactive oxygen species Reactive oxygen species
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| GB/T 7714 | Ke, Mei-Rong , Wang, Chao , He, Qinxue et al. N-bridging tetra-substituted zinc(II) phthalocyanines with Q-band absorption up to 780 nm and eminent photosensitizing activities for photodynamic therapy [J]. | DYES AND PIGMENTS , 2024 , 227 . |
| MLA | Ke, Mei-Rong et al. "N-bridging tetra-substituted zinc(II) phthalocyanines with Q-band absorption up to 780 nm and eminent photosensitizing activities for photodynamic therapy" . | DYES AND PIGMENTS 227 (2024) . |
| APA | Ke, Mei-Rong , Wang, Chao , He, Qinxue , Que, Rongbin , Wei, Ying , Zheng, Bi-Yuan et al. N-bridging tetra-substituted zinc(II) phthalocyanines with Q-band absorption up to 780 nm and eminent photosensitizing activities for photodynamic therapy . | DYES AND PIGMENTS , 2024 , 227 . |
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Background Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect.Methods Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane.Results When the upper part of a mouse brain was irradiated using a laser (0.2 W cm(- 2)) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway.Conclusion This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas.
Keyword ：
Albumin binding Albumin binding Blood-brain-barrier Blood-brain-barrier Glioma Glioma Photosensitizer Photosensitizer Secreted protein acidic and rich in cysteine Secreted protein acidic and rich in cysteine
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| GB/T 7714 | Li, Xingshu , Oh, Jae Sang , Lee, Yoonji et al. Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway [J]. | BIOMATERIALS RESEARCH , 2023 , 27 (1) . |
| MLA | Li, Xingshu et al. "Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway" . | BIOMATERIALS RESEARCH 27 . 1 (2023) . |
| APA | Li, Xingshu , Oh, Jae Sang , Lee, Yoonji , Lee, Eun Chae , Yang, Mengyao , Kwon, Nahyun et al. Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway . | BIOMATERIALS RESEARCH , 2023 , 27 (1) . |
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Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O-2(center dot-)) and singlet oxygen (O-1(2)) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g(-1) PcSA) and light dose (30 J cm(-2)). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.
Keyword ：
anticancer anticancer fluorescence imaging fluorescence imaging liposome liposome photodynamic therapy photodynamic therapy phthalocyanine phthalocyanine
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| GB/T 7714 | Chen, Zixuan , Zhao, Yuan-Yuan , Li, Li et al. A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects [J]. | MOLECULES , 2023 , 28 (5) . |
| MLA | Chen, Zixuan et al. "A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects" . | MOLECULES 28 . 5 (2023) . |
| APA | Chen, Zixuan , Zhao, Yuan-Yuan , Li, Li , Li, Ziqing , Fu, Shuwen , Xu, Yihui et al. A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects . | MOLECULES , 2023 , 28 (5) . |
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In order to reduce the intramolecular charge-transfer (ICT) effect of amine groups on the photophysical properties of zinc (II) phthalocyanine (ZnPc), tertiary amines were covalently connected with ZnPc ring via ethyl phydroxybenzoate or diethyl 5-hydroxyisophthalate. Six new tertiary amine-modified ZnPcs were therefore synthesized and characterized. Meanwhile, the corresponding quaternary ammonium ZnPcs were also synthesized. The effects of different substitution ways (mono-substitutions, symmetrical tetra-substitutions, or asymmetric tetra-substitutions) and the numbers of different substitutions on the photophysical and physicochemical properties of these ZnPcs were studied. All twelve ZnPcs had relatively high singlet oxygen quantum yields (& phi;& UDelta; = 0.32-0.68) and fluorescence quantum yields (& phi;F = 0.23-0.40), where the amine-containing substituents did not show obvious ICT effect. All ZnPcs showed effective phototoxicity towards breast cancer cells (IC50 = 63-366 nmol/L). Among them, three tetra-substituted ZnPcs containing quaternary ammonium groups (4aN, 4bN and 4cN) showed the best in vitro anticancer photodynamic activities with IC50 = 64-76 nmol/L, which owned to their relatively high cellular uptake. The tumor inhibition rate of 4aN on H22 tumor-bearing mice reached 87% (4aN dose: 3 nmol/g; light dose: 685 nm, 135 J/cm2).
Keyword ：
Cancer Cancer Photodynamic therapy Photodynamic therapy Photosensitizer Photosensitizer Phthalocyanine Phthalocyanine Structure-activity relationship Structure-activity relationship
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| GB/T 7714 | Zhang, Ling , Zhao, Yuan-Yuan , Chen, Zi-Xuan et al. Synthesis, characterization and photodynamic antitumor activity of amine-modified zinc (II) phthalocyanines [J]. | DYES AND PIGMENTS , 2023 , 218 . |
| MLA | Zhang, Ling et al. "Synthesis, characterization and photodynamic antitumor activity of amine-modified zinc (II) phthalocyanines" . | DYES AND PIGMENTS 218 (2023) . |
| APA | Zhang, Ling , Zhao, Yuan-Yuan , Chen, Zi-Xuan , Cheng, Yun-Tong , Zheng, Bi-Yuan , Ke, Mei-Rong et al. Synthesis, characterization and photodynamic antitumor activity of amine-modified zinc (II) phthalocyanines . | DYES AND PIGMENTS , 2023 , 218 . |
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Unlike traditional methods of modifying phthalocyanines (Pcs), we herein report a smart and visible way to switch the aromaticity of silicon(iv) phthalocyanines via a reversible nucleophilic addition reaction of the Pc skeleton induced by alkalis and acids, leading to an interesting allochroism phenomenon and the switching of photosensitive activities.
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| GB/T 7714 | Ke, Mei-Rong , Chen, Zixuan , Shi, Jie et al. A smart and visible way to switch the aromaticity of silicon(iv) phthalocyanines [J]. | CHEMICAL COMMUNICATIONS , 2023 , 59 (65) : 9832-9835 . |
| MLA | Ke, Mei-Rong et al. "A smart and visible way to switch the aromaticity of silicon(iv) phthalocyanines" . | CHEMICAL COMMUNICATIONS 59 . 65 (2023) : 9832-9835 . |
| APA | Ke, Mei-Rong , Chen, Zixuan , Shi, Jie , Wei, Ying , Liu, Hao , Huang, Shuping et al. A smart and visible way to switch the aromaticity of silicon(iv) phthalocyanines . | CHEMICAL COMMUNICATIONS , 2023 , 59 (65) , 9832-9835 . |
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