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学者姓名：刘见永
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Abstract ：
Chemiluminescence (CL) is a self-illuminating phenomenon fueled by chemical energy instead of extra excited light, which features superiority in sensitivity, signal-to-background ratios, and imaging depth. Strategies to synthesize a CL emission unimolecular skeleton in the second near-infrared window (NIR-II) and a unimolecular probe with direct duplex NIR-II [CL/fluorescence (FL)] emission are lacking. Here, we employ modular synthesis routes to construct a series of directly activated NIR-II CL emission unimolecular probes with a maximum emission wavelength of up to 1060 nm, and use them for real-time and continuous detection of the superoxide anion generated in acetaminophen induced liver injury in a female mice model under both NIR-II CL and NIR-II FL imaging channels. Thus, this study establishes a directly activatable NIR-II CL emission unimolecular skeleton, validating the scalability of this duplex NIR-II CL/FL imaging platform in bioactive molecule detection and disease diagnosis.
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| GB/T 7714 | Chen, Zhongxiang , Li, Qian , Wu, Ying et al. Molecular Engineering of Direct Activated NIR-II Chemiluminescence Platform for In Vivo Chemiluminescence-fluorescence Duplex Imaging [J]. | NATURE COMMUNICATIONS , 2025 , 16 (1) . |
| MLA | Chen, Zhongxiang et al. "Molecular Engineering of Direct Activated NIR-II Chemiluminescence Platform for In Vivo Chemiluminescence-fluorescence Duplex Imaging" . | NATURE COMMUNICATIONS 16 . 1 (2025) . |
| APA | Chen, Zhongxiang , Li, Qian , Wu, Ying , Liu, Jianyong , Liu, Luntao , Su, Lichao et al. Molecular Engineering of Direct Activated NIR-II Chemiluminescence Platform for In Vivo Chemiluminescence-fluorescence Duplex Imaging . | NATURE COMMUNICATIONS , 2025 , 16 (1) . |
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Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate 6 to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound 7, which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate 6 predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC50 value of 3.01 mu M. A distinct preference for HepG2 cells over HELF cells is observed with conjugate 6 but not with compound 7. In vivo experiments further confirm that conjugate 6 has a specific affinity for tumor tissues, and the combination treatment of conjugate 6 with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.
Keyword ：
BODIPY BODIPY erlotinib erlotinib photodynamic therapy photodynamic therapy photosensitizer photosensitizer reactive oxygen species reactive oxygen species
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| GB/T 7714 | Wu, Wenqiang , Luo, Chengmiao , Zhu, Chunhui et al. A Novel Boron Dipyrromethene-Erlotinib Conjugate for Precise Photodynamic Therapy against Liver Cancer [J]. | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2024 , 25 (12) . |
| MLA | Wu, Wenqiang et al. "A Novel Boron Dipyrromethene-Erlotinib Conjugate for Precise Photodynamic Therapy against Liver Cancer" . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 25 . 12 (2024) . |
| APA | Wu, Wenqiang , Luo, Chengmiao , Zhu, Chunhui , Cai, Zhengyan , Liu, Jianyong . A Novel Boron Dipyrromethene-Erlotinib Conjugate for Precise Photodynamic Therapy against Liver Cancer . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2024 , 25 (12) . |
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The development of a highly effective and low toxic drug is very beneficial for precise cancer therapy. Herein, taking advantage of the hypoxic nature of tumors, we carefully designed and synthesized the first hypoxiaactivated single -molecule prodrug BDP-CPT-NO 2 for fluorescence imaging -guided chemo-photothermal dualmode therapy. The prodrug contains the chemotherapeutic drug camptothecin (CPT) and a boron dipyrromethene (BDP)-based photothermal agent, which are connected through a nitroreductase (NTR)-responsive linker (a nitro unit), and shows no fluorescence and extremely low cytotoxicity under normoxia. However, the nitro in the prodrug could be reduced to amino by exogenous NTR with nicotinamide adenine dinucleotide (NADH) in PBS buffer solution and endogenous NTR in hypoxic cancer cells, which is followed by a self-immolative reaction that leads to the release of CPT and BDP-COOH. This process is accompanied by significantly enhanced BDP and CPT fluorescence, which are due to NTR-induced ester-to-carboxylate conversion and fluorescence resonance energy transfer (FRET) interruption, respectively. Concomitantly, BDP-CPT-NO 2 displays powerful combined chemo-PTT therapeutic efficacy, as evidenced in human cervical cancer HeLa and human liver cancer HepG2 cells, as well as in mice bearing H22 tumors. This study provides a promising strategy for effective and selective cancer treatment by hypoxia-activated prodrugs caged within organic photothermal agents.
Keyword ：
Boron dipyrromethene Boron dipyrromethene Combination therapy Combination therapy Hypoxia-responsive Hypoxia-responsive Photothermal therapy Photothermal therapy Prodrug Prodrug
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| GB/T 7714 | Weng, Xiao-Lu , Luo, Cheng-Miao , Gao, Tian-Jiao et al. Hypoxia-activated prodrug combining site-specific chemotherapy and light-driven photothermal therapy [J]. | SENSORS AND ACTUATORS B-CHEMICAL , 2024 , 415 . |
| MLA | Weng, Xiao-Lu et al. "Hypoxia-activated prodrug combining site-specific chemotherapy and light-driven photothermal therapy" . | SENSORS AND ACTUATORS B-CHEMICAL 415 (2024) . |
| APA | Weng, Xiao-Lu , Luo, Cheng-Miao , Gao, Tian-Jiao , Yang, Xiao-Zhen , Liu, Qinying , Liu, Jian-Yong . Hypoxia-activated prodrug combining site-specific chemotherapy and light-driven photothermal therapy . | SENSORS AND ACTUATORS B-CHEMICAL , 2024 , 415 . |
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The emergence of chemoresistance poses a significant challenge to the efficacy of DNA-damaging agents in cancer treatment, in part due to the inherent DNA repair capabilities of cancer cells. The Ku70/80 protein complex (Ku) plays a central role in double-strand breaks (DSBs) repair through the classical non-homologous end joining (c-NHEJ) pathway, and has proven to be one of the most promising drug target for cancer treatment when combined with radiotherapy or chemotherapy. In this study, we conducted a high-throughput screening of small-molecule inhibitors targeting the Ku complex by using a fluorescence polarization-based DNA binding assay. From a library of 11,745 small molecules, UMI-77 was identified as a potent Ku inhibitor, with an IC50 value of 2.3 mu M. Surface plasmon resonance and molecular docking analyses revealed that UMI-77 directly bound the inner side of Ku ring, thereby disrupting Ku binding with DNA. In addition, UMI-77 also displayed potent inhibition against MUS81-EME1, a key player in homologous recombination (HR), demonstrating its potential for blocking both NHEJ- and HR-mediated DSB repair pathways. Further cell-based studies showed that UMI-77 could impair bleomycin-induced DNA damage repair, and significantly sensitized multiple cancer cell lines to the DNA-damaging agents. Finally, in a mouse xenograft tumor model, UMI-77 significantly enhanced the chemotherapeutic efficacy of etoposide with little adverse physiological effects. Our work offers a new avenue to combat chemoresistance in cancer treatment, and suggests that UMI-77 could be further developed as a promising candidate in cancer treatment.
Keyword ：
Anticancer Anticancer Chemosensitivity Chemosensitivity DNA repair DNA repair Ku70 Ku70 Ku80 Ku80 NHEJ NHEJ Small-molecule inhibitor Small-molecule inhibitor UMI-77 UMI-77
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| GB/T 7714 | Chen, Xuening , Chen, Changkun , Luo, Chengmiao et al. Discovery of UMI-77 as a novel Ku70/80 inhibitor sensitizing cancer cells to DNA damaging agents in vitro and in vivo [J]. | EUROPEAN JOURNAL OF PHARMACOLOGY , 2024 , 975 . |
| MLA | Chen, Xuening et al. "Discovery of UMI-77 as a novel Ku70/80 inhibitor sensitizing cancer cells to DNA damaging agents in vitro and in vivo" . | EUROPEAN JOURNAL OF PHARMACOLOGY 975 (2024) . |
| APA | Chen, Xuening , Chen, Changkun , Luo, Chengmiao , Liu, Jianyong , Lin, Zhonghui . Discovery of UMI-77 as a novel Ku70/80 inhibitor sensitizing cancer cells to DNA damaging agents in vitro and in vivo . | EUROPEAN JOURNAL OF PHARMACOLOGY , 2024 , 975 . |
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Chemiluminescence (CL) with the elimination of excitation light and minimal autoflu-orescence interference has been wieldy applied in biosensing and bioimaging. However, the traditional emission of CL probes was mainly in the range of 400 to 650 nm, leading to undesired resolution and penetration in a biological object. Therefore, it was urgent to develop CL molecules in the near-infrared window [NIR, including NIR-I (650 to 900 nm) and near-infrared-II (900 to 1,700 nm)], coupled with unique advantages of long-time imaging, sensitive response, and high resolution at depths of millimeters. However, no NIR-II CL unimolecular probe has been reported until now. Herein, we developed an H2S-activated NIR-II CL probe [chemiluminiscence donor 950, (CD -950)] by covalently connecting two Schaap's dioxetane donors with high chemical energy to a NIR-II fluorophore acceptor candidate via intramolecular CL resonance energy transfer strategy, thereby achieving high efficiency of 95%. CD-950 exhibited superior capacity including long-duration imaging (-60 min), deeper tissue penetration (-10 mm), and specific H2S response under physiological conditions. More importantly, CD-950 showed detection capability for metformin-induced hepatotoxicity with 2.5 -fold higher signal-to-background ratios than that of NIR-II fluorescence mode. The unimolecular NIR-II CL probe holds great potential for the evaluation of drug-induced side effects by tracking its metabolites in vivo, further facilitating the rational design of novel NIR-II CL-based detection platforms.
Keyword ：
bioimaging bioimaging chemiluminescence chemiluminescence H2S H2S metformin-induced hepatotoxicity metformin-induced hepatotoxicity second near-infrared window second near-infrared window
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| GB/T 7714 | Chen, Zhongxiang , Su, Lichao , Wu, Ying et al. Design and synthesis of a small molecular NIR-II chemiluminescence probe for in vivo-activated H2S imaging [J]. | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA , 2023 , 120 (8) . |
| MLA | Chen, Zhongxiang et al. "Design and synthesis of a small molecular NIR-II chemiluminescence probe for in vivo-activated H2S imaging" . | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 120 . 8 (2023) . |
| APA | Chen, Zhongxiang , Su, Lichao , Wu, Ying , Liu, Jianyong , Wu, Rongrong , Li, Qian et al. Design and synthesis of a small molecular NIR-II chemiluminescence probe for in vivo-activated H2S imaging . | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA , 2023 , 120 (8) . |
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Human serum albumin (HSA) and hydrazine (N2H4) are known biomarkers and damage agents of liver function activity, respectively. However, the mechanism of association between HSA and N2H4 in the liver remains unexplored. Herein, we report a naphthalimide-based smart fluorescent probe NI-2 for the N2H4 mediated cascade detection of HSA (N2H4 boolean AND HSA). Results showed that the levulinate recognition group on NI-2 is ammonolyzed within seconds in response to N2H4, releasing the compound NI-OH, triggering a hypsochromic shift of the emission to 400 nm; while with the coexistence of HSA, the entry of NI-OH into the hydrophobic cavity of HSA, resulting a bathochromic emission shift to 670 nm. We have further revealed the reaction mechanism of NI-2 cascade reacting with N2H4 boolean AND HSA through HRMS, replacement experiment and molecular docking method. NI-2 has been successfully applied in detecting N2H4 boolean AND HSA in human urine quantitatively and N2H4 in water samples or plants. A qualitative test paper strip model for quick response of N2H4 and N2H4 boolean AND HSA has also been established. Moreover, NI-2 can be applied in bioimaging of HepG2 cells and zebrafish, indicating that NI-2 can be a potential tool for the study of liver damage.
Keyword ：
Bioimaging in cells and zebrafish Bioimaging in cells and zebrafish Cascade reaction Cascade reaction Human serum albumin and hydrazine Human serum albumin and hydrazine Paper strip Paper strip Smartfluorescent probe Smartfluorescent probe
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| GB/T 7714 | Ke, Yue , Wei, Di , Lu, Ziyao et al. A smart probe for multi-analyte signaling: Cascade detection of HSA mediated by N2H4 [J]. | SENSORS AND ACTUATORS B-CHEMICAL , 2023 , 395 . |
| MLA | Ke, Yue et al. "A smart probe for multi-analyte signaling: Cascade detection of HSA mediated by N2H4" . | SENSORS AND ACTUATORS B-CHEMICAL 395 (2023) . |
| APA | Ke, Yue , Wei, Di , Lu, Ziyao , Cao, Jing , Liu, Jianyong , Fu, Nanyan . A smart probe for multi-analyte signaling: Cascade detection of HSA mediated by N2H4 . | SENSORS AND ACTUATORS B-CHEMICAL , 2023 , 395 . |
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Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at similar to 720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at similar to 800 nm, resulting in the PA(800)/PA(720) ratio. In vitro, a linear relationship is successfully established between PA(800)/PA(720) values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo. Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.
Keyword ：
biosensing biosensing molecule molecule photoacousticimaging photoacousticimaging prodrug prodrug ratiometric ratiometric
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| GB/T 7714 | Wang, Shuai , Fu, Qinrui , Su, Lichao et al. Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging [J]. | ACS SENSORS , 2023 , 8 (12) : 4737-4746 . |
| MLA | Wang, Shuai et al. "Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging" . | ACS SENSORS 8 . 12 (2023) : 4737-4746 . |
| APA | Wang, Shuai , Fu, Qinrui , Su, Lichao , Wu, Ying , Zhu, Kang , Yang, De-Chao et al. Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging . | ACS SENSORS , 2023 , 8 (12) , 4737-4746 . |
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Photothermal therapy (PTT) has gained extensive interest in tumor treatments due to its non-invasive and low -toxic nature. However, the currently available photothermal agents (PTAs) mostly show unsatisfactory photo -thermal conversion efficiency (PCE). Besides, as a local cancer treatment modality, PTT fails to inhibit metastasis of tumors. To address these issues, in this study, two aza-boron-dipyrromethene (aza-BODIPY)-based organic photothermal agents (OPTAs), Fc-aza-BODIPY and TPA-aza-BODIPY, were rationally coined by introducing two strong electron-donating ferrocene (Fc) moieties and two triphenylamine (TPA) rotors, which could boost intramolecular photo-induced electron transfer (PET) and molecular rotation respectively, thereby improving the PCE of aza-BODIPY dyes. After encapsulation of hydrophobic Fc-aza-BODIPY (or TPA-aza-BODIPY) and quercetin with biodegradable PLGA and DSPE-mPEG2000, the resulting nanoparticles (FAQ NPs and TAQ NPs) showed excellent optical properties with PCE of-72.0% and-79.7% and specific tumor accumulations through enhanced permeability and retention (EPR) effects. Consequently, these two NPs possessed prominent antitumor effects under 880 nm laser irradiation. Moreover, both FAQ NPs and TAQ NPs loaded with quercetin could inhibit tumor metastasis efficiently. These two multifunctional nanomaterials integrating OPTAs and anti -metastasis agents constructed a cooperative treatment program, which may provide a potential opportunity for future clinical cancer treatment.
Keyword ：
aza-BODIPY aza-BODIPY Metastasis Metastasis Multifunctional nanomaterials Multifunctional nanomaterials Photothermal conversion efficiency Photothermal conversion efficiency Photothermal therapy Photothermal therapy Quercetin Quercetin
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| GB/T 7714 | Yang, Xiao-Zhen , Wen, Lin-Feng , Xu, Gan et al. Multifunctional organic nanomaterials with ultra-high photothermal conversion efficiency for photothermal therapy and inhibition of cancer metastasis [J]. | BIOORGANIC CHEMISTRY , 2023 , 130 . |
| MLA | Yang, Xiao-Zhen et al. "Multifunctional organic nanomaterials with ultra-high photothermal conversion efficiency for photothermal therapy and inhibition of cancer metastasis" . | BIOORGANIC CHEMISTRY 130 (2023) . |
| APA | Yang, Xiao-Zhen , Wen, Lin-Feng , Xu, Gan , Lin, Hao-Hua , Wang, Shuai , Liu, Jian-Yong . Multifunctional organic nanomaterials with ultra-high photothermal conversion efficiency for photothermal therapy and inhibition of cancer metastasis . | BIOORGANIC CHEMISTRY , 2023 , 130 . |
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Optical imaging in the second near-infrared (NIR-II, 900-1700 nm) window has been extensively investigated for bioimaging. However, a strong autofluorescence background from real-time excitation light significantly reduces the images' quality of NIR-II fluorescence (FL) imaging. To resolve this issue, a NIR-II self-luminous small molecule (CLPD) based on bioluminescence (BL) resonance energy transfer (BRET) mechanism is first developed. The reactive oxygen species (ROS) can trigger NIR-II BL and reduce the NIR-II FL signals of the CLPD simultaneously, enabling ROS-correlated ratiometric BL/FL imaging. CLPD is used for high-contrast NIR-II BL imaging of osteoarthritis as well as guiding the treatment process by ratiometric BL/FL imaging. Moreover, CLPD is applied for NIR-II BL imaging of tumor triggered by the generated ROS during PDT. A correlation between the ratiometric NIR-II BL/FL signal and tumor size is constructed, providing a trustworthy tool for early assessment of PDT effect. Overall, this study presents a novel NIR-II self-luminous small molecular probe for in vivo imaging and provides a strategy for design a self-evaluation system of therapeutic effect.
Keyword ：
activatable probes activatable probes bioluminescence bioluminescence biosensing biosensing in vivo bioimaging in vivo bioimaging NIR-II imaging NIR-II imaging
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| GB/T 7714 | Yuan, Meng , Fang, Xiao , Liu, Jianyong et al. NIR-II Self-Luminous Molecular Probe for In Vivo Inflammation Tracking and Cancer PDT Effect Self-Evaluating [J]. | SMALL , 2022 , 19 (11) . |
| MLA | Yuan, Meng et al. "NIR-II Self-Luminous Molecular Probe for In Vivo Inflammation Tracking and Cancer PDT Effect Self-Evaluating" . | SMALL 19 . 11 (2022) . |
| APA | Yuan, Meng , Fang, Xiao , Liu, Jianyong , Yang, Kaiqiong , Xiao, Shenggan , Yang, Sheng et al. NIR-II Self-Luminous Molecular Probe for In Vivo Inflammation Tracking and Cancer PDT Effect Self-Evaluating . | SMALL , 2022 , 19 (11) . |
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Hypoxia-activated prodrugs (HAPs) have drawn increasing attention for improving the antitumor effects while minimizing side effects. However, the heterogeneous distribution of the hypoxic region in tumors severely impedes the curative effect of HAPs. Additionally, most HAPs are not amenable to optical imaging, and it is difficult to precisely trace them in tissues. Herein, we carefully designed and synthesized a multifunctional therapeutic BAC prodrug by connecting the chemotherapeutic drug camptothecin (CPT) and the fluorescent photothermal agent boron dipyrromethene (BODIPY) via hypoxia-responsive azobenzene linkers. To enhance the solubility and tumor accumulation, the prepared BAC was further encapsulated into a human serum albumin (HSA)-based drug delivery system to form HSA@BAC nanoparticles. Since the CPT was caged by a BODIPY-based molecule at the active site, the BAC exhibited excellent biosafety. Importantly, the activated CPT could be quickly released from BAC and could perform chemotherapy in hypoxic cancer cells, which was ascribed to the cleavage of the azobenzene linker by overexpressed azoreductase. After irradiation with a 730 nm laser, HSA@BAC can efficiently generate hyperthermia to achieve irreversible cancer cell death by oxygen-independent photothermal therapy. Under fluorescence imaging-guided local irradiation, both in vitro and in vivo studies demonstrated that HSA@BAC exhibited superior antitumor effects with minimal side effects.
Keyword ：
BODIPY BODIPY fluorescence imaging fluorescence imaging hypoxia-activated prodrug hypoxia-activated prodrug nanoparticle nanoparticle photothermal therapy photothermal therapy
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| GB/T 7714 | Yang, De-Chao , Wen, Lin-Feng , Du, Liyang et al. A Hypoxia-Activated Prodrug Conjugated with a BODIPY-Based Photothermal Agent for Imaging-Guided Chemo-Photothermal Combination Therapy [J]. | ACS APPLIED MATERIALS & INTERFACES , 2022 , 14 (36) : 40546-40558 . |
| MLA | Yang, De-Chao et al. "A Hypoxia-Activated Prodrug Conjugated with a BODIPY-Based Photothermal Agent for Imaging-Guided Chemo-Photothermal Combination Therapy" . | ACS APPLIED MATERIALS & INTERFACES 14 . 36 (2022) : 40546-40558 . |
| APA | Yang, De-Chao , Wen, Lin-Feng , Du, Liyang , Luo, Cheng-Miao , Lu, Zi-Yao , Liu, Jian-Yong et al. A Hypoxia-Activated Prodrug Conjugated with a BODIPY-Based Photothermal Agent for Imaging-Guided Chemo-Photothermal Combination Therapy . | ACS APPLIED MATERIALS & INTERFACES , 2022 , 14 (36) , 40546-40558 . |
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