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学者姓名：薛金萍
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Abstract ：
The major challenges in photodynamic therapy (PDT) are the neutralization of cytotoxic reactive oxygen species (ROS) by the excessive antioxidant glutathione (GSH) in tumor cells, high self-aggregation of most photosensitizers (PSs), and long time to protect from light after treatment. Thus, to develop the molecular PSs for the improved and safe PDT in clinic, a novel and versatile PS (Mal-Pc) has been designed by di-substituting maleimides to the axial positions of silicon (IV) phthalocyanine. Owning to the conjugation of maleimides, Mal-Pc can not only entry tumor cells more easily and faster, but also can react with the intracellular overexpressed GSH after entry. In addition, upon electrophilic reaction with GSH, the inhibition of self-aggregation of Mal-Pc has been demonstrated by the restoration of the fluorescence emission in aqueous media. As a result, the intracellular ROS levels and photocytotoxicity of Mal-Pc are dramatically enhanced. Finally, the high hydrophilicity of the product GS-conjugates facilitates Mal-Pc eliminate from the normal cells more rapidly. Overall, this work revealed the high potential of the versatile molecular Mal-Pc for highly efficient and safe PDT in clinical translation.
Keyword ：
Glutathione Glutathione Maleimides Maleimides Photodynamic therapy Photodynamic therapy Phthalocyanine Phthalocyanine
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| GB/T 7714 | Chen, Juanjuan , Yan, Meiqi , Huang, Kunshan et al. Novel molecular photosensitizer with simultaneously GSH depletion, aggregation inhibition and accelerated elimination for improved and safe photodynamic therapy [J]. | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 2023 , 245 . |
| MLA | Chen, Juanjuan et al. "Novel molecular photosensitizer with simultaneously GSH depletion, aggregation inhibition and accelerated elimination for improved and safe photodynamic therapy" . | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 245 (2023) . |
| APA | Chen, Juanjuan , Yan, Meiqi , Huang, Kunshan , Xue, Jinping . Novel molecular photosensitizer with simultaneously GSH depletion, aggregation inhibition and accelerated elimination for improved and safe photodynamic therapy . | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 2023 , 245 . |
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Abstract ：
本发明公开了一种靶向Mcl‑1酶的锌酞菁3‑氯‑6甲基苯并[b]噻吩‑2‑羧酸轭合物及其制备方法，属于药物化学技术领域。以3‑硝基邻苯二甲腈为原始原料，通过亲核反应得到3‑(4‑羧基甲酯苯氧基)邻苯二腈，再通过成环反应和亲核反应生成1‑(4‑羧基苯氧基)酞菁，最后通过亲核取代反应生成目标产物锌酞菁3‑氯‑6甲基苯并[b]噻吩‑2‑羧酸轭合物。该轭合物能增强对于三阴性乳腺癌细胞的杀伤作用，为提高光动力治疗提供新思路。
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| GB/T 7714 | 陈涓涓 , 薛金萍 , 黄坤山 . 靶向Mcl-1酶的锌酞菁3-氯-6甲基苯并[b]噻吩-2-羧酸轭合物及其制备方法 : CN202210103571.2[P]. | 2022-01-28 00:00:00 . |
| MLA | 陈涓涓 et al. "靶向Mcl-1酶的锌酞菁3-氯-6甲基苯并[b]噻吩-2-羧酸轭合物及其制备方法" : CN202210103571.2. | 2022-01-28 00:00:00 . |
| APA | 陈涓涓 , 薛金萍 , 黄坤山 . 靶向Mcl-1酶的锌酞菁3-氯-6甲基苯并[b]噻吩-2-羧酸轭合物及其制备方法 : CN202210103571.2. | 2022-01-28 00:00:00 . |
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As one of the most malignant breast cancer types, triple-negative breast cancer (TNBC) treatment is a particularly great challenge in the current era of precision medicine. Due to the limited effectiveness and targeting of current treatment methods, it is urgently need to develop an effective precision strategy to combat TNBC. Herein, a novel TNBC targeted molecular drug based on zinc(II) phthalocyanine (BF-Pc) was rationally designed by conjugating a Pim-1 kinase inhibitor with high TNBC selectivity. In our in vitro investigation, BF-Pc not only exhibits extremely high targeting to TNBC cells overexpressed Pim-1 kinases, but also shows ultra-efficient photocytotoxicity toward TNBC cells far beyond the normal cells. Significantly, BF-Pc-induced PDT can obviously suppress TNBC cell migration and invasion. The proposed manner in our work offers a promising approach to combat TNBC effectively and precisely.
Keyword ：
Invasion Invasion Migration Migration Photodynamic therapy Photodynamic therapy Pim-1 kinase Pim-1 kinase Targeting Targeting Triple -negative breast cancer Triple -negative breast cancer
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| GB/T 7714 | Huang, Kunshan , Yang, Si , Zhang, Yalan et al. A novel Pim-1 kinase-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy and reduced metastasis [J]. | DYES AND PIGMENTS , 2022 , 207 . |
| MLA | Huang, Kunshan et al. "A novel Pim-1 kinase-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy and reduced metastasis" . | DYES AND PIGMENTS 207 (2022) . |
| APA | Huang, Kunshan , Yang, Si , Zhang, Yalan , Xue, Jinping , Chen, Juanjuan . A novel Pim-1 kinase-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy and reduced metastasis . | DYES AND PIGMENTS , 2022 , 207 . |
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As a third-generation steroidal aromatase inhibitor, exemestane (EXE) has been clinically used for postmenopausal advanced breast cancer patients whose condition has progressed after treatment of tamoxifen. However, the further development and application of EXE was limited due to its low solubility and oral bioavailability, inevitable drug resistance and side effects. Based on the unique therapeutic advantages of photodynamic therapy (PDT), a novel aromatase-targeted photosensitizer EX-Pc was synthesized by the combination of EXE and the phthalocyanine photosensitizer. The compound EX-Pc still maintains the superior optical properties of the phthalocyanine photosensitizer upon the introduction of EXE and triethylene glycol chain. Meanwhile, the results of targeted uptake in vitro and in vivo indicated that EX-Pc exhibited high selectivity and affinity for breast cancer cells and tumor tissues, which have the overexpression of aromatase. More importantly, the compound EX-Pc exhibits significant photocytotoxicity and tumor regression ability on breast cancer cells and tumor. In addition, the compound EX-Pc shows negligible side effects and high biological safety. We believe that this is a potential strategy for the treatment of postmenopausal breast cancer.
Keyword ：
Aromatase Aromatase Breast cancer Breast cancer Exemestane Exemestane Photodynamic therapy Photodynamic therapy Photosensitizer Photosensitizer
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| GB/T 7714 | Yuan, Gankun , Wang, Qilu , Huang, Kunshan et al. An aromatase inhibitor in combination with Zinc(II) phthalocyanine for targeted therapy of post-menopausal breast cancer [J]. | DYES AND PIGMENTS , 2022 , 202 . |
| MLA | Yuan, Gankun et al. "An aromatase inhibitor in combination with Zinc(II) phthalocyanine for targeted therapy of post-menopausal breast cancer" . | DYES AND PIGMENTS 202 (2022) . |
| APA | Yuan, Gankun , Wang, Qilu , Huang, Kunshan , Xue, Jinping , Chen, Juanjuan . An aromatase inhibitor in combination with Zinc(II) phthalocyanine for targeted therapy of post-menopausal breast cancer . | DYES AND PIGMENTS , 2022 , 202 . |
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Photodynamic therapy (PDT), as an alternative non-invasive clinical treatment modality, has been extensively employed for various anticancer applications in preclinical and clinical trials. However, there is hardly any PDT research based on invasive or metastatic tumors. But it can't be ignored that cancer metastases are responsible for 90% of all cancer-related death. Among these metastatic cancers, prostate cancer (PCa) is regarded as one of the leading causes of cancer related deaths amongst male patients due to its high metastasis and high fatality rate. At present, it remains a great challenge to apply traditional PDT technology for inhibiting prostate cancer metastasis. In this work, we successfully designed and synthesized a novel MAO-A targeted photosensitizer Pc-MLB for targeted photodynamic treatment of prostate cancer and inhibiting its metastasis in vitro. In vitro ex-periments demonstrate that Pc-MLB shows high target affinity and specificity towards prostate cancer cells and remarkable photodynamic anticancer activity compared with the control. More significantly, the migration and invasion assays show that Pc-MLB exhibits the ability to inhibit the migration and metastasis of prostate cancer cells to some extent.
Keyword ：
Anticancer Anticancer Anti-metastasis Anti-metastasis Monoamine oxidase-A Monoamine oxidase-A Photodynamic therapy Photodynamic therapy Phthalocyanine Phthalocyanine
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| GB/T 7714 | Zhao, Xuan , Wang, Qilu , Jia, Xiao et al. A monoamine oxidase-A inhibitor phthalocyanine conjugate for targeted photodynamic therapy and inhibition of prostate cancer metastasis in vitro [J]. | DYES AND PIGMENTS , 2022 , 207 . |
| MLA | Zhao, Xuan et al. "A monoamine oxidase-A inhibitor phthalocyanine conjugate for targeted photodynamic therapy and inhibition of prostate cancer metastasis in vitro" . | DYES AND PIGMENTS 207 (2022) . |
| APA | Zhao, Xuan , Wang, Qilu , Jia, Xiao , Xue, Jinping , Chen, Juanjuan . A monoamine oxidase-A inhibitor phthalocyanine conjugate for targeted photodynamic therapy and inhibition of prostate cancer metastasis in vitro . | DYES AND PIGMENTS , 2022 , 207 . |
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Photodynamic therapy (PDT) is a promising and non-invasive treatment for various cancers. Although nuclear PDT has considerable therapeutic prospects, it is still hindered by the non-specific recognition of tumor tissues or the degradation of nuclear targeting cationic groups by enzymes in the blood. Herein, a hierarchical targeted and controlled release strategy is proposed by using folate-modified poly-beta-cyclodextrin (poly-beta-CD) as a nano-carrier for loading nuclear localization signals (NLSs)-conjugated photosensitizer PAP (PAP = pyropheophorbide a-PAAKRVKLD). Excitingly, the obtained FA-CD@PAP (FA = folic acid) and nanoparticles (NPs) can specifically recognize tumor cells overexpressing folate receptors (FR) to remarkedly enhance the intracellular accumulation. Furthermore, the encapsulated PAP can be released under acidic conditions to realize precise nuclear localization. The reactive oxygen species (ROS) generated by the intranuclear-accumulated PAP upon irradiation can oxidize and destroy DNA chains or DNA repair enzymes instantaneously, which can directly induce cell death. As a result, FA-CD@PAP NPs exhibit excellent tumor regression and negligible side effects. This work provides an intelligent nuclear-targeted delivery strategy for in situ nuclear PDT with extremely prominent efficacy and high biological safety.
Keyword ：
hierarchical targeted hierarchical targeted nuclear localization signal nuclear localization signal nuclear-targeted nuclear-targeted photodynamic therapy photodynamic therapy poly-beta-cyclodextrin poly-beta-cyclodextrin
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| GB/T 7714 | Yuan, Gankun , Wang, Qilu , You, Zifan et al. A novel hierarchical targeting and controllable smart nanoparticles for enhanced in situ nuclear photodynamic therapy [J]. | NANO RESEARCH , 2022 , 15 (5) : 4212-4223 . |
| MLA | Yuan, Gankun et al. "A novel hierarchical targeting and controllable smart nanoparticles for enhanced in situ nuclear photodynamic therapy" . | NANO RESEARCH 15 . 5 (2022) : 4212-4223 . |
| APA | Yuan, Gankun , Wang, Qilu , You, Zifan , Chen, Xuening , Xue, Jinping , Jia, Xiao et al. A novel hierarchical targeting and controllable smart nanoparticles for enhanced in situ nuclear photodynamic therapy . | NANO RESEARCH , 2022 , 15 (5) , 4212-4223 . |
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Multi-modal synergistic therapy, especially the integration of near-infrared laser phototherapies and chemo-therapy, is often sought after owing to its minimal invasiveness, low side effects, and improved anticancer therapeutic efficacy. Herein, CuS nanoparticles were first coated with zinc phthalocya-nine derivant (Pc)-functionalized mesoporous silica (mSiO2-Pc) to achieve a drug delivery system (CuS@mSiO2-Pc) with photo-thermal/photodynamic therapy. Chemical drug DOX was subsequently loaded for chemotherapy, and hyaluronic acid (HA) was employed as a covering material with cancer targeting. The as-obtained CuS@mSiO2-Pc(DOX)@HA nanoparticles were nano-sized with good biocompatibility, effective DOX loading, and controllable DOX releasing. Expectedly, this multifunctional nanoplatform exhibits effective generation of reactive oxygen species and hyperthermia upon the near-infrared laser irradiation. Most importantly, the nanoparticles were targeted into 4T1 cells and showed significantly remarkable cytotoxicity under near -infrared laser irradiation, proving their synergistic therapeutic efficacy. Therefore, this targeted drug system based on CuS with synergistic photothermal therapy/photodynamic therapy/chemotherapy has great application prospects in clinical anticancer treatment for triple negative breast cancer.
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| GB/T 7714 | Lv, Huihui , Zhu, Yuchao , Xue, Jinping et al. Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer [J]. | LANGMUIR , 2022 . |
| MLA | Lv, Huihui et al. "Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer" . | LANGMUIR (2022) . |
| APA | Lv, Huihui , Zhu, Yuchao , Xue, Jinping , Jia, Xiao , Chen, Juanjuan . Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer . | LANGMUIR , 2022 . |
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Tumor acidic environment-activated combination therapy holds great promise to significantly decrease side effects, circumvent multiple drug resistance, and improve therapeutic outcomes for cancer treatment. Herein, Sorafenib/ZnPc(PS)(4)@Fe-III-TA nanoparticles (SPFT) are designed with acid-environment turned-on fluorescence to report the activation of triple therapy including photodynamic, chemodynamic, and chemotherapy on hepatocellular carcinoma. The SPFT are composed of SP cores formulated via self-assembly of sorafenib and ZnPc(PS)(4), with high drug loading efficiency, and Fe-III-TA shells containing FeCl3 and tannic acid. Importantly, the nanoparticles suppress reactive oxygen species (ROS) generation of ZnPc(PS)(4) due to their formation in nanoparticles, while assisting simultaneous uptake of the uploaded drugs in cancer cells. The tumor acidic environment initiates Fe-III-TA decomposition and accelerates a chemodynamic reaction between Fe(II )and H2O2 to generate toxic center dot OH. Then, the SP core is decomposed to separate ZnPc(PS)(4) and sorafenib, which leads to fluorescence turning-on of ZnPc(PS)(4), expedited photodynamic reactions, and burst release of sorafenib. Notably, SPFT shows low dark cytotoxicity to normal cells but exerts high potency on hepatocellular carcinoma cells under near-infrared light irradiation, which is much more potent than either sorafenib or ZnPc(PS)(4) alone. This research offers a facile nanomedicine design strategy for cancer therapy.
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| GB/T 7714 | Yao, Mengyu , Wang, Xiaojie , Huang, Kunshan et al. Fluorescence-Reporting-Guided Tumor Acidic Environment-Activated Triple Photodynamic, Chemodynamic, and Chemotherapeutic Reactions for Efficient Hepatocellular Carcinoma Cell Ablation [J]. | LANGMUIR , 2022 , 38 (18) : 5381-5391 . |
| MLA | Yao, Mengyu et al. "Fluorescence-Reporting-Guided Tumor Acidic Environment-Activated Triple Photodynamic, Chemodynamic, and Chemotherapeutic Reactions for Efficient Hepatocellular Carcinoma Cell Ablation" . | LANGMUIR 38 . 18 (2022) : 5381-5391 . |
| APA | Yao, Mengyu , Wang, Xiaojie , Huang, Kunshan , Jia, Xiao , Xue, Jinping , Guo, Bing et al. Fluorescence-Reporting-Guided Tumor Acidic Environment-Activated Triple Photodynamic, Chemodynamic, and Chemotherapeutic Reactions for Efficient Hepatocellular Carcinoma Cell Ablation . | LANGMUIR , 2022 , 38 (18) , 5381-5391 . |
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Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive ox-ygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and in-vasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.
Keyword ：
IDO IDO Immunotherapy Immunotherapy Indoximod Indoximod Photodynamic therapy Photodynamic therapy Photosensitizer Photosensitizer Triple negative breast cancer Triple negative breast cancer
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| GB/T 7714 | Huang, Kunshan , Yan, Meiqi , Zhang, Han et al. A phthalocyanine-based photosensitizer for effectively combating triple negative breast cancer with enhanced photodynamic anticancer activity and immune response [J]. | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 2022 , 241 . |
| MLA | Huang, Kunshan et al. "A phthalocyanine-based photosensitizer for effectively combating triple negative breast cancer with enhanced photodynamic anticancer activity and immune response" . | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 241 (2022) . |
| APA | Huang, Kunshan , Yan, Meiqi , Zhang, Han , Xue, Jinping , Chen, Juanjuan . A phthalocyanine-based photosensitizer for effectively combating triple negative breast cancer with enhanced photodynamic anticancer activity and immune response . | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 2022 , 241 . |
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As growth factor receptor-2 (HER-2), progesterone receptor (PR) and estrogen receptor (ER) are scarce in triple -negative breast cancer (TNBC), it is a great challenge to combat TNBC with high tumor specificity and thera-peutic efficacy. Most traditional treatments including surgical resection, chemotherapy, and radiotherapy would more or less cause serious side effects and drug resistance. Photodynamic therapy (PDT) has huge potential in the treatment of TNBC for minimal invasiveness, low toxicity, less drug resistance and high spatiotemporal selec-tivity. Inspired by the advantages of small-molecule-targeted PDT and the sensitization effect of myeloid cell leukemia-1 (MCL-1) inhibitor, a novel photosensitizer BC-Pc was designed by conjugating MCL-1 inhibitor with zinc phthalocyanines. Owning to 3-chloro-6-methyl-1-benzothiophene-2-carboxylic acid (BC) moiety, BC-Pc exhibits the high affinity towards MCL-1 and reduce its self-aggregation in TNBC cells. Therefore, MCL-1 targeted BC-Pc showed remarkable intracellular fluorescence and ROS generation in TNBC cells. Additionally, BC-Pc can selectively sensitize TNBC cells to ROS-induced damage, resulting in improved therapeutic effect to TNBC cells and negligible toxicity to normal cells. More importantly, BC-Pc can effectively inhibit the migration and in-vasion of TNBC cells, and enhance immune response, all of which will be beneficial to eradicate TNBC. To the best of our knowledge, BC-Pc is the novel MCL-targeted photosensitizer, which owns the amplified ROS-induced lethality and anticancer immune response for TNBC. Overall, our study provides a promising strategy to achieve targeting and highly efficient therapy of TNBC.
Keyword ：
Immunotherapy Immunotherapy MCL-1 MCL-1 Photodynamic therapy Photodynamic therapy Photosensitizer Photosensitizer Phthalocyanine Phthalocyanine Triple negative breast cancer Triple negative breast cancer
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| GB/T 7714 | Huang, Kunshan , Yao, Huiqiao , Yan, Meiqi et al. A MCL-1-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy, sensitization to ROS-induced damage, and immune response [J]. | JOURNAL OF INORGANIC BIOCHEMISTRY , 2022 , 237 . |
| MLA | Huang, Kunshan et al. "A MCL-1-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy, sensitization to ROS-induced damage, and immune response" . | JOURNAL OF INORGANIC BIOCHEMISTRY 237 (2022) . |
| APA | Huang, Kunshan , Yao, Huiqiao , Yan, Meiqi , Zhang, Han , Yuan, Gankun , Wang, Qilu et al. A MCL-1-targeted photosensitizer to combat triple-negative breast cancer with enhanced photodynamic efficacy, sensitization to ROS-induced damage, and immune response . | JOURNAL OF INORGANIC BIOCHEMISTRY , 2022 , 237 . |
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