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学者姓名：陈琪
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Abstract ：
Proteolysis-targeting chimeras (PROTACs) are dual-functional molecules composed of a protein of interest (POI) ligand and an E3 ligase ligand connected by a linker, which can recruit POI and E3 ligases simultaneously, thereby inducing the degradation of POI and showing great potential in disease treatment. A challenge in developing PROTACs is the design of linkers and the modification of ligands to establish a multifunctional platform that enhances degradation efficiency and antitumor activity. As a programmable and modifiable nanomaterial, DNA tetrahedron can precisely assemble and selectively recognize molecules and flexibly adjust the distance between molecules, making them ideal linkers. Herein, we developed a multivalent PROTAC based on a DNA tetrahedron, named AS-TD2-PRO. Using DNA tetrahedron as a linker, we combined modules targeting tumor cells, recognizing E3 ligases, and multiple POI together. We took the undruggable target protein signal transducer and activator of transcription 3 (STAT3), associated with the etiology and progression in a variety of malignant tumors, as an example in this study. AS-TD2-PRO with two STAT3 recognition modules demonstrated good potential in enhancing tumor-specific targeting and degradation efficiency compared to traditional bivalent PROTACs. Furthermore, in a mouse tumor model, the superior therapeutic activity of AS-TD2-PRO was observed. Overall, DNA tetrahedron-driven multivalent PROTACs both serve as a proof of principle for multifunctional PROTAC design and introduce a promising avenue for cancer treatment strategies.
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| GB/T 7714 | Li, Shiqing , Zeng, Tao , Wu, Zhixing et al. DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting [J]. | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2025 , 147 (2) : 2168-2181 . |
| MLA | Li, Shiqing et al. "DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting" . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147 . 2 (2025) : 2168-2181 . |
| APA | Li, Shiqing , Zeng, Tao , Wu, Zhixing , Huang, Jiabao , Cao, Xiuping , Liu, Yana et al. DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2025 , 147 (2) , 2168-2181 . |
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Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain’s natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles. © 2024 by the authors.
Keyword ：
brain-targeted brain-targeted drug delivery system drug delivery system glioma glioma PAMAM dendrimers PAMAM dendrimers
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| GB/T 7714 | Yan, X. , Chen, Q. . Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy [J]. | Polymers , 2024 , 16 (14) . |
| MLA | Yan, X. et al. "Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy" . | Polymers 16 . 14 (2024) . |
| APA | Yan, X. , Chen, Q. . Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy . | Polymers , 2024 , 16 (14) . |
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Cancer immunotherapy is an attractive strategy because it stimulates immune cells to target malignant cells by regulating the intrinsic activity of the immune system. However, due to lacking many immunologic markers, it remains difficult to treat glioma, a representative "cold" tumor. Herein, to wake the "hot" tumor immunity of glioma, Porphyromonas gingivalis (Pg) is customized with a coating to create an immunogenic tumor microenvironment and further prove the effect in combination with the immune checkpoint agent anti-PD-1, exhibiting elevated therapeutic efficacy. This is accomplished not by enhancing the delivery of PD-1 blockade to enhance the effect of immunotherapy, but by introducing bacterial photothermal therapy to promote greater involvement of M1 cells in the immune response. After reaching glioma, the bacteria further target glioma cells and M2 phenotype macrophages selectively, enabling precise photothermal conversion for lysing tumor cells and M2 phenotype macrophages, which thereby enhances the positive feedback loop of cancer cells-M1 macrophages-T cells. Collectively, the bacteria synergized with PD-1 blockade strategy may be the key to overcoming the immunosuppressive glioma microenvironment and improving the outcome of immunotherapy toward glioma. Porphyromonas gingivalis (Pg) synergized with PD-1 blockade strategy is reported. After reaching glioma, the customized bacteria can target glioma cells and M2 phenotype macrophages selectively, receive and convert light into heat for lysing tumor cells and M2 phenotype macrophages, thereby enhancing the positive feedback loop of cancer cells-M1 macrophages-T cells. image
Keyword ：
anti-PD-1 anti-PD-1 cancer immunotherapy cancer immunotherapy customized bacteria customized bacteria glioma glioma tumor microenvironment tumor microenvironment
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| GB/T 7714 | Chen, Qi , Zheng, Yuyi , Chen, Xiaojie et al. Bacteria Synergized with PD-1 Blockade Enhance Positive Feedback Loop of Cancer Cells-M1 Macrophages-T Cells in Glioma [J]. | ADVANCED SCIENCE , 2024 , 11 (20) . |
| MLA | Chen, Qi et al. "Bacteria Synergized with PD-1 Blockade Enhance Positive Feedback Loop of Cancer Cells-M1 Macrophages-T Cells in Glioma" . | ADVANCED SCIENCE 11 . 20 (2024) . |
| APA | Chen, Qi , Zheng, Yuyi , Chen, Xiaojie , Xing, Yuan , Zhang, Jiajie , Yan, Xinyi et al. Bacteria Synergized with PD-1 Blockade Enhance Positive Feedback Loop of Cancer Cells-M1 Macrophages-T Cells in Glioma . | ADVANCED SCIENCE , 2024 , 11 (20) . |
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In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood-brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug delivery systems have been widely studied and applied to the study of cerebral ischemic diseases due to their favorable biocompatibility, high efficiency, strong specificity, and specific targeting ability. In this paper, we briefly describe the pathological process of reperfusion injuries in strokes and focus on the therapeutic research progress of nano-drug delivery systems in ischemic strokes, aiming to provide certain references to understand the progress of research on nano-drug delivery systems (NDDSs).
Keyword ：
blood-brain barrier blood-brain barrier ischemic stroke ischemic stroke nano-drug delivery system nano-drug delivery system nanoparticles nanoparticles
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| GB/T 7714 | Zhang, Jiajie , Chen, Zhong , Chen, Qi . Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke [J]. | MOLECULES , 2024 , 29 (8) . |
| MLA | Zhang, Jiajie et al. "Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke" . | MOLECULES 29 . 8 (2024) . |
| APA | Zhang, Jiajie , Chen, Zhong , Chen, Qi . Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke . | MOLECULES , 2024 , 29 (8) . |
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With the rapid development of drug delivery systems, extracellular vesicles (EVs) have emerged as promising stars for improving targeting abilities and realizing effective delivery. Numerous studies have shown when compared to conventional strategies in targeted drug delivery (TDD), EVs-based strategies have several distinguished advantages besides targeting, such as participating in cell-to-cell communications and immune response, showing high biocompatibility and stability, penetrating through biological barriers, etc. In this review, we mainly focus on the mass production of EVs including the challenges and strategies for scaling up EVs production in a cost-effective and reproducible manner, the loading and active targeting methods, and examples of EVs as vehicles for TDD in consideration of potential safety and regulatory issues associated. We also conclude and discuss the rigor and reproducibility of EVs production, the current research status of the application of EVs-based strategies to targeted drug delivery, clinical conversion prospects, and existing chances and challenges.
Keyword ：
carrier carrier drug delivery system drug delivery system Extracellular vesicles Extracellular vesicles nanoparticle nanoparticle
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| GB/T 7714 | Chen, Qi , Zheng, Yuyi , Jiang, Xuhong et al. Nature's carriers: leveraging extracellular vesicles for targeted drug delivery [J]. | DRUG DELIVERY , 2024 , 31 (1) . |
| MLA | Chen, Qi et al. "Nature's carriers: leveraging extracellular vesicles for targeted drug delivery" . | DRUG DELIVERY 31 . 1 (2024) . |
| APA | Chen, Qi , Zheng, Yuyi , Jiang, Xuhong , Wang, Yi , Chen, Zhong , Wu, Di . Nature's carriers: leveraging extracellular vesicles for targeted drug delivery . | DRUG DELIVERY , 2024 , 31 (1) . |
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Abstract ：
Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain's natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles.
Keyword ：
brain-targeted brain-targeted drug delivery system drug delivery system glioma glioma PAMAM dendrimers PAMAM dendrimers
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| GB/T 7714 | Yan, Xinyi , Chen, Qi . Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy [J]. | POLYMERS , 2024 , 16 (14) . |
| MLA | Yan, Xinyi et al. "Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy" . | POLYMERS 16 . 14 (2024) . |
| APA | Yan, Xinyi , Chen, Qi . Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy . | POLYMERS , 2024 , 16 (14) . |
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Abstract ：
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| GB/T 7714 | Yan, X. , Chen, Q. . Self-oxygenating hydrogel: Regulation of postsurgical tumor recurrence/metastasis and wound healing [J]. | MedComm - Oncology , 2024 , 3 (2) . |
| MLA | Yan, X. et al. "Self-oxygenating hydrogel: Regulation of postsurgical tumor recurrence/metastasis and wound healing" . | MedComm - Oncology 3 . 2 (2024) . |
| APA | Yan, X. , Chen, Q. . Self-oxygenating hydrogel: Regulation of postsurgical tumor recurrence/metastasis and wound healing . | MedComm - Oncology , 2024 , 3 (2) . |
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An endogenous time-keeping system found in all kingdoms of life, the endogenous circadian clock, is the source of the essential cyclic change mechanism known as the circadian rhythm. The primary circadian clock that synchronizes peripheral circadian clocks to the proper phase is housed in the anterior hypothalamus's suprachiasmatic nuclei (SCN), which functions as a central pacemaker. According to many epidemiological studies, many cancer types, especially brain tumors, have shown evidence of dysregulated clock gene expression, and the connection between clock and brain tumors is highly specific. In some studies, it is reported that the treatment administered in the morning has been linked to prolonged survival for brain cancer patients, and drug sensitivity and gene expression in gliomas follow daily rhythms. These results suggest a relationship between the circadian rhythm and the onset and spread of brain tumors, while further accumulation of research evidence will be needed to establish definitely these positive outcomes as well as to determine the mechanism underlying them. Chronotherapy provides a means of harnessing current medicines to prolong patients' lifespans and improve their quality of life, indicating the significance of circadian rhythm in enhancing the design of future patient care and clinical trials. Moreover, it is implicated that chronobiological therapy target may provide a significant challenge that warrants extensive effort to achieve. This review examines evidence of the relationship of circadian rhythm with glioma molecular pathogenesis and summarizes the mechanisms and drugs implicated in this disease.
Keyword ：
Brain tumor Brain tumor Chronotherapy Chronotherapy Circadian rhythms Circadian rhythms Mechanism Mechanism Therapeutic drug Therapeutic drug
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| GB/T 7714 | Zou, Shuang , Chen, Qi , Shen, Zhiwei et al. Update on the roles of regular daily rhythms in combating brain tumors [J]. | EUROPEAN JOURNAL OF PHARMACOLOGY , 2024 , 986 . |
| MLA | Zou, Shuang et al. "Update on the roles of regular daily rhythms in combating brain tumors" . | EUROPEAN JOURNAL OF PHARMACOLOGY 986 (2024) . |
| APA | Zou, Shuang , Chen, Qi , Shen, Zhiwei , Qin, Bing , Zhu, Xiangdong , Lan, Yulong . Update on the roles of regular daily rhythms in combating brain tumors . | EUROPEAN JOURNAL OF PHARMACOLOGY , 2024 , 986 . |
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