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学者姓名：陈海军
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Abstract ：
Despite significant advances in diverse cancer treatment methods, chemotherapy remains the primary approach, and the development of chemoresistance is still a persistent problem during treatment. Here, we developed a derivative of the natural product mangiferin as a carrier for delivering chemotherapeutic drug, aiming to overcome drug resistance through a distinctive four-pronged strategy, including modulation of inflammatory tumor microenvironment (TME), induction of ferroptosis, deep tumor penetration, and the combinatory anticancer effects. After clarifying the promotion effects of the cancer associated fibroblasts (CAFs) in chemoresistance, and leveraging our previous elucidation of the anti-inflammatory and ferroptosis-inducing ability of mangiferin, we synthesized mangiferin amphiphile (MMF) and developed a self-assembled carrier-free nanomedicine, named MP, through the self-assembly of MMF and the representative chemotherapeutic drug paclitaxel (PTX). MP possessed a particle size of approximately 68 nm with compact filamentous nanostructures. MP demonstrated efficient tumor-targeting and deep tumor penetration abilities. Furthermore, MP effectively suppressed glutathione peroxidase 4 (GPX4) expression to induce ferroptosis, mitigated the activation of IL-6/STAT3 pathway to deactivate CAFs within the inflammatory TME, and exhibited robust anti-cancer effects against PTXresistant breast cancer both in vitro and in vivo. This mangiferin derivative represents a promising "all-in-one" nanocarrier for delivering chemotherapeutic drugs, offering a green, safe, and convenient self-assembled carrierfree nanomedicine to effectively overcome drug resistance.
Keyword ：
CAFs CAFs Carrier-free nanomedicine Carrier-free nanomedicine Drug resistance Drug resistance Ferroptosis Ferroptosis Inflammatory tumor microenvironment Inflammatory tumor microenvironment
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| GB/T 7714 | Zheng, Yilin , Xu, Ruofei , Chen, Tingyan et al. Four-pronged reversal of chemotherapy resistance by mangiferin amphiphile [J]. | JOURNAL OF CONTROLLED RELEASE , 2025 , 378 : 776-790 . |
| MLA | Zheng, Yilin et al. "Four-pronged reversal of chemotherapy resistance by mangiferin amphiphile" . | JOURNAL OF CONTROLLED RELEASE 378 (2025) : 776-790 . |
| APA | Zheng, Yilin , Xu, Ruofei , Chen, Tingyan , Wang, Ya , Chen, Xiaoye , Chen, Haijun et al. Four-pronged reversal of chemotherapy resistance by mangiferin amphiphile . | JOURNAL OF CONTROLLED RELEASE , 2025 , 378 , 776-790 . |
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Heptamethine indocyanine dyes (HMICDs) have excellent near-infrared (NIR) properties and are capable of converting light energy into heat energy under NIR laser irradiation, enabling their use in photothermal therapy (PTT) of tumors. However, their photostability is poor, and they are easily inactivated by photobleaching after prolonged and repeated exposure to NIR laser. In addition, unmodified HMICDs have poor water solubility and tend to aggregate, limiting their biological applications. Herein, we designed and synthesized HMICDs with hydrophilic side chains and different substituent groups on polymethine chain, and explored the effects of these modifications on the water solubility, photostability and photothermal properties of the dyes. The introduction of tri-ethylene glycol hydrophilic side chains can improve the water solubility of HMICDs, and enhance the photostability and photothermal properties by increasing the spatial hindrance of the dyes. Furthermore, the incorporation of substituents with strong electron-withdrawing ability into the polymethine chain can improve the photostability and photothermal effect of the dyes. Under laser irradiation, the dyes can inhibit the proliferation of tumor cells by enhancing intracellular reactive oxygen species levels, decreasing mitochondrial membrane potential, and inducing cell apoptosis. In two tumor-bearing mouse models, dye 11 can effectively inhibit tumor growth by exerting photothermal effects with good biosafety. This work can provide a research foundation for the subsequent construction of HMICDs-based photothermal therapeutic agents for clinical applications.
Keyword ：
Heptamethine indocyanine dyes Heptamethine indocyanine dyes Photostability Photostability Photothermal therapy Photothermal therapy Water solubility Water solubility
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| GB/T 7714 | Shen, Xinyi , Yu, Jing , Chen, Tingyan et al. Structural modification of heptamethine indocyanine dyes with improved aqueous solubility and stability for photothermal therapy [J]. | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 2025 , 290 . |
| MLA | Shen, Xinyi et al. "Structural modification of heptamethine indocyanine dyes with improved aqueous solubility and stability for photothermal therapy" . | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 290 (2025) . |
| APA | Shen, Xinyi , Yu, Jing , Chen, Tingyan , Sun, Xianbin , Long, Haixin , Du, Manyi et al. Structural modification of heptamethine indocyanine dyes with improved aqueous solubility and stability for photothermal therapy . | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 2025 , 290 . |
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The challenging treatment outcomes for nonsmall cell lung cancer (NSCLC) necessitate the development of innovative therapeutic strategies. In this work, we developed a multifunctional nanoplatform by modifying mesoporous silica nanoparticles (MSNs) with an aptamer (Apt) targeting epidermal growth factor (EFGR), and coloading a sonosensitizer, hematoporphyrin (HP), along with the natural nitric oxide (NO) donor, l-arginine (l-Arg). The resulting Apt-modified MSN loaded with l-Arg and HP (designated as AMLH) was designed for the targeted gas-assisted sonodynamic therapy (SDT) of NSCLC. AMLH exhibited an appropriate particle size, good drug loading ability, and ultrasound-responsive drug release. The coloading of HP and l-Arg resulted in higher encapsulation efficiency compared to single-drug loading, and AMLH remained stable when stored at 4 degrees C for 15 days. AMLH was capable of generating reactive oxygen species (ROS) and NO under ultrasound stimulation, leading to the further production of peroxynitrite (ONOO-). AMLH demonstrated specific targeting and recognition of EGFR-positive NSCLC cells, with preincubation of free Apt reducing cellular uptake, confirming the specificity of the Apt-functionalized nanoparticles. Cellular distribution studies revealed that AMLH was primarily localized in lysosomes after internalization. MTT assays and live/dead cell staining confirmed the superior cytotoxicity of AMLH, which effectively inhibits cell proliferation through mitochondrial membrane potential collapse and nuclear damage under ultrasound stimulation. These results highlight the combined efficacy of EGFR targeting, SDT, and NO gas therapy, offering a promising strategy to improve the NSCLC treatment outcomes.
Keyword ：
aptamer aptamer nitricoxide nitricoxide nonsmallcell lung cancer nonsmallcell lung cancer peroxynitrite peroxynitrite sonodynamic therapy sonodynamic therapy
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| GB/T 7714 | Zheng, Fangying , Zhang, Peixia , Zhang, Yinglu et al. Aptamer-Modified Mesoporous Silica Nanoparticle for Nitric Oxide-Enhanced Targeted Sonodynamic Therapy against Lung Cancer [J]. | ACS APPLIED NANO MATERIALS , 2025 , 8 (10) : 5179-5192 . |
| MLA | Zheng, Fangying et al. "Aptamer-Modified Mesoporous Silica Nanoparticle for Nitric Oxide-Enhanced Targeted Sonodynamic Therapy against Lung Cancer" . | ACS APPLIED NANO MATERIALS 8 . 10 (2025) : 5179-5192 . |
| APA | Zheng, Fangying , Zhang, Peixia , Zhang, Yinglu , Long, Haixin , Zhu, Fangyin , Chen, Haijun et al. Aptamer-Modified Mesoporous Silica Nanoparticle for Nitric Oxide-Enhanced Targeted Sonodynamic Therapy against Lung Cancer . | ACS APPLIED NANO MATERIALS , 2025 , 8 (10) , 5179-5192 . |
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The therapeutic effectiveness of photothermal therapy (PTT) is limited by heat tolerance and PTT-induced inflammation, which increases the risk of tumor metastasis and recurrence. Ferroptosis combined with PTT can achieve significant therapeutic effects. In this work, we designed self-healing photothermal nanotherapeutics to achieve effective PTT with triple-amplified ferroptosis and cascade inflammation inhibition after photothermal treatment. After the ferroptosis-inducing ability of mangiferin (MF) was first elucidated, the nanocomplex PFeM, coordinated by Fe3+ and MF with polyvinylpyrrolidone (PVP) modification, was prepared by a one-pot self-assembly method. PFeM with laser irradiation could induce intensified ferroptosis by integrating the functions of MF to deactivate glutathione peroxidase 4, Fe3+/Fe2+ to generate lethal reactive oxygen species via the Fenton reaction, and the photothermal effect to amplify ferroptosis. More importantly, the released MF could achieve cascade inflammation inhibition, thereby reversing the proinflammatory microenvironment caused by PTT. The in vivo antitumor and anti-inflammatory effects of PFeM were further confirmed in a 4T1 tumor-bearing mouse model. This study expounding the ferroptosis-inducing effects of MF and utilizing the strategy of chelating MF with iron ions can provide a new idea for developing photothermal nanoagents with clinically convertible safety ingredients and a green preparation process that improve efficacy and reduce adverse reactions during PTT. © 2024 American Chemical Society.
Keyword ：
Laser safety Laser safety Pathology Pathology Reactive oxygen species Reactive oxygen species
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| GB/T 7714 | Zheng, Yilin , Zheng, Fangying , Xu, Ruofei et al. Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition [J]. | ACS Applied Materials and Interfaces , 2024 , 16 (39) : 51994-52007 . |
| MLA | Zheng, Yilin et al. "Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition" . | ACS Applied Materials and Interfaces 16 . 39 (2024) : 51994-52007 . |
| APA | Zheng, Yilin , Zheng, Fangying , Xu, Ruofei , Sun, Xianbin , Yu, Jing , Chen, Haijun et al. Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition . | ACS Applied Materials and Interfaces , 2024 , 16 (39) , 51994-52007 . |
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An efficient and rapid protocol for the oxidative halogenation of tryptamines with 10 % aqueous NaClO has been developed. This reaction is featured by its operational simplicity, metal-free conditions, no purification, and high yield. Notably, the resulting key intermediates are suitable for further functionalization with various nucleophiles, including amines, N-aromatic heterocycles, indoles and phenols. The overall transformation exhibits broad functional-group tolerance and is applicable to the late-stage functionalization of complex biorelevant molecules. © 2024 Wiley-VCH GmbH.
Keyword ：
Autophagy Autophagy Drug discovery Drug discovery Green chemistry Green chemistry Late-stage functionalization Late-stage functionalization Tryptamines Tryptamines
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| GB/T 7714 | Xu, J. , Zhang, Y. , Cai, Q. et al. Green Late-Stage Functionalization of Tryptamines [J]. | Chemistry - A European Journal , 2024 , 30 (46) . |
| MLA | Xu, J. et al. "Green Late-Stage Functionalization of Tryptamines" . | Chemistry - A European Journal 30 . 46 (2024) . |
| APA | Xu, J. , Zhang, Y. , Cai, Q. , Chen, L. , Sun, Y. , Liu, Q. et al. Green Late-Stage Functionalization of Tryptamines . | Chemistry - A European Journal , 2024 , 30 (46) . |
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Abstract ：
An efficient and rapid protocol for the oxidative halogenation of tryptamines with 10 % aqueous NaClO has been developed. This reaction is featured by its operational simplicity, metal-free conditions, no purification, and high yield. Notably, the resulting key intermediates are suitable for further functionalization with various nucleophiles, including amines, N-aromatic heterocycles, indoles and phenols. The overall transformation exhibits broad functional-group tolerance and is applicable to the late-stage functionalization of complex biorelevant molecules. An efficient and rapid protocol for the oxidative halogenation of tryptamines with 10 % aqueous NaClO has been developed. This reaction is featured by its operational simplicity, metal-free conditions, no purification, and high yield. The overall transformation exhibits broad functional-group tolerance and is applicable to the late-stage functionalization of complex biorelevant molecules. image
Keyword ：
Autophagy Autophagy Drug discovery Drug discovery Green chemistry Green chemistry Late-stage functionalization Late-stage functionalization Tryptamines Tryptamines
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| GB/T 7714 | Xu, Jiayi , Zhang, Yahui , Cai, Qiling et al. Green Late-Stage Functionalization of Tryptamines [J]. | CHEMISTRY-A EUROPEAN JOURNAL , 2024 , 30 (46) . |
| MLA | Xu, Jiayi et al. "Green Late-Stage Functionalization of Tryptamines" . | CHEMISTRY-A EUROPEAN JOURNAL 30 . 46 (2024) . |
| APA | Xu, Jiayi , Zhang, Yahui , Cai, Qiling , Chen, Li , Sun, Yang , Liu, Qinying et al. Green Late-Stage Functionalization of Tryptamines . | CHEMISTRY-A EUROPEAN JOURNAL , 2024 , 30 (46) . |
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Here we report a highly efficient method for coupling of peroxypyrroloindolenines with amines under catalyst-free conditions to obtain stable C2-N peroxyindolenines in high yields with remarkable functional group tolerance. Initial studies have shown that compound 13 exhibits potent inhibition of the B16/F10 cell line with an IC50 value of 2.18 mu M.
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| GB/T 7714 | Zheng, Xiaoshan , Wang, Menghan , Sun, Xianbin et al. Catalyst-free coupling of peroxypyrroloindolenines with amines to afford stable peroxyindolenines [J]. | ORGANIC & BIOMOLECULAR CHEMISTRY , 2024 , 23 (5) : 1215-1218 . |
| MLA | Zheng, Xiaoshan et al. "Catalyst-free coupling of peroxypyrroloindolenines with amines to afford stable peroxyindolenines" . | ORGANIC & BIOMOLECULAR CHEMISTRY 23 . 5 (2024) : 1215-1218 . |
| APA | Zheng, Xiaoshan , Wang, Menghan , Sun, Xianbin , Gao, Yu , Chen, Haijun . Catalyst-free coupling of peroxypyrroloindolenines with amines to afford stable peroxyindolenines . | ORGANIC & BIOMOLECULAR CHEMISTRY , 2024 , 23 (5) , 1215-1218 . |
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Modulating the immunosuppressive tumor immune microenvironment (TIME) is considered a promising strategy for cancer treatment. However, effectively modulating the immunosuppressive TIME within hypoxic zones remains a significant challenge. In this work, we developed a hypoxia-responsive amphiphilic drug carrier using boron-dipyrromethene (BODIPY) dye-modified chitosan (CsB), and then fabricated a hypoxia-targeted nanotheranostic system, named CsBPNs, through self-assembly of CsB and pexidartinib (5-((5-Chloro-1H-pyrrolo[2,3b ]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl), PLX3397), an immunotherapeutic drug targeting tumor-associated macrophages (TAMs), for synergistic photothermal/immunotherapy and hypoxia imaging. CsBPNs demonstrated uniform size, good stability, and hypoxia-switchable fluorescence and photo- thermal effects, enabling deep penetration and hypoxia imaging capacities in three-dimensional tumor cell spheres and tumor tissues. In vitro and in vivo experiments showed that CsBPNs under laser irradiation promoted TAMs repolarization, reversed the immunosuppressive TIME, and enhanced the therapeutic outcome of PLX3397 in solid tumors by facilitating deep delivery into hypoxic regions and synergistic photothermal therapy. This work provides a new strategy for detecting and modulating the immunosuppressive TIME in hypoxic zones, potentially enabling more precise and effective photo-immunotherapy in the future.
Keyword ：
BODIPY BODIPY Hypoxia-responsive Hypoxia-responsive Immunotherapy Immunotherapy Nanotheranostics Nanotheranostics Photothermal therapy Photothermal therapy
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| GB/T 7714 | Li, Xudong , Sun, Xianbin , Wang, Ya et al. A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation [J]. | JOURNAL OF COLLOID AND INTERFACE SCIENCE , 2024 , 678 : 897-912 . |
| MLA | Li, Xudong et al. "A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation" . | JOURNAL OF COLLOID AND INTERFACE SCIENCE 678 (2024) : 897-912 . |
| APA | Li, Xudong , Sun, Xianbin , Wang, Ya , Chen, Haijun , Gao, Yu . A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation . | JOURNAL OF COLLOID AND INTERFACE SCIENCE , 2024 , 678 , 897-912 . |
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The emergence of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) poses formidable obstacles to non-small cell lung cancer (NSCLC) therapy. Real-time monitoring of the efficacy of EGFR-TKIs to avoid invalid treatment remains a great challenge. Herein, we rationally designed a EGFR-TKImodified liposomal complex co-loaded with a iodine-containing contrast agent ioversol (IOV) and a photosensitizer indocyanine green (ICG), namely ELIG, for simultaneous EGFR-TKI-mediated computed tomography/ fluorescence dual-modal imaging to monitor drug resistance during the treatment, and combined photodynamic therapy (PDT) and photothermal therapy (PTT) to reverse drug resistance. ELIG exhibited good physicochemical properties, favorable photothermal effects, and high singlet oxygen production. ELIG can protect ICG and IOV from rapid degradation and prolong the circulation time. In addition, ELIG had a great ability to recognize drugsensitive EGFR-mutated NSCLC cells, and could monitor the changes in the intracellular amounts of the imaging agents to detect the drug resistance and predict the efficacy during the treatments. Additionally, the heavy atom effect of IOV can increase the PDT effect of ICG obviously. With 808 nm laser irradiation, ELIG showed satisfactory anticancer effects to reverse drug resistance by the synergism of PDT and PTT in vitro and in vivo. Hence, this work holds great promise for providing a new idea and an effective strategy for predicting and managing the efficacy of EGFR-TKIs.
Keyword ：
Drug resistance detection Drug resistance detection Liposomal complexes Liposomal complexes Molecular targeted therapy Molecular targeted therapy Nanotheranostics Nanotheranostics Phototherapy Phototherapy
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| GB/T 7714 | Yang, Ya , Li, Xiumei , Long, Haixin et al. Multifunctional liposomal complex for detection of the acquired resistance to EGFR-TKIs and synergistic anticancer phototherapy [J]. | APPLIED MATERIALS TODAY , 2024 , 38 . |
| MLA | Yang, Ya et al. "Multifunctional liposomal complex for detection of the acquired resistance to EGFR-TKIs and synergistic anticancer phototherapy" . | APPLIED MATERIALS TODAY 38 (2024) . |
| APA | Yang, Ya , Li, Xiumei , Long, Haixin , Cheng, Yuntong , Zheng, Yilin , Chen, Haijun et al. Multifunctional liposomal complex for detection of the acquired resistance to EGFR-TKIs and synergistic anticancer phototherapy . | APPLIED MATERIALS TODAY , 2024 , 38 . |
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Herein, we report a general approach to effectively construct C-N or C-C spiroindolines using tetrahydro-beta-carbolines as starting materials via a rearrangement coupling reaction. This method is characterized by its operational simplicity and mild conditions. Notably, a wide range of anilines and indoles are suitable for this intermolecular coupling, yielding the corresponding C-N or C-C spiroindolines in good to excellent yields.
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| GB/T 7714 | Liu, Xiaoling , Qiao, Panpan , Chen, Hui et al. Synthesis of C-N or C-C Spiroindolines via Rearrangement Coupling Reaction [J]. | ORGANIC LETTERS , 2024 , 26 (45) : 9759-9763 . |
| MLA | Liu, Xiaoling et al. "Synthesis of C-N or C-C Spiroindolines via Rearrangement Coupling Reaction" . | ORGANIC LETTERS 26 . 45 (2024) : 9759-9763 . |
| APA | Liu, Xiaoling , Qiao, Panpan , Chen, Hui , Gao, Yu , Chen, Haijun . Synthesis of C-N or C-C Spiroindolines via Rearrangement Coupling Reaction . | ORGANIC LETTERS , 2024 , 26 (45) , 9759-9763 . |
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