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Size and Charge Dual-Switchable Nanoparticles for Achieving Chemosensitization and Immune Infiltration against Pancreatic Ductal Adenocarcinoma

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ADVANCED FUNCTIONAL MATERIALS 2025年第1期35卷

作者： Song, Haolin Chen, Hongyi Chen, Qinjun Fan, Hongrui li, Chufeng Wang, Yu Zhang, Shilin li, xuwen Su, Boyu Sun, Tao Jiang, Chen Fudan Univ Sch Pharm Dept Pharmaceut Key Lab Smart Drug DeliveryMinist EducState Key Shanghai 201203 Peoples R China MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China Fujian Med Univ Affiliated Hosp 1 Natl Reg Med Ctr Dept Digest Dis Binhai Campus Fuzhou 350212 Peoples R China

Pancreatic ductal adenocarcinoma (PDAC), one of the most challenging cancers, is uniquely characterized by a biological barrier composed of multiple components in the extracellular matrix, preventing penetration of chemotherapeutic agents and hindering clinical drug treatment. Collagen I arrangement is critical. In this study, gemcitabine is chosen as the chemotherapeutic agent and dasatinib as the collagen-I-disrupting agent. When collagen I arrangement is disrupted, not only the chemotherapeutic drug enters the tumor area better, but the infiltration of CD8+ T cells into the tumor also increases. Therefore, a hypoxia-responsive linker-crosslinked polymer, DGD/L@GBI, is designed, which can be simultaneously loaded with two therapeutic agents, gemcitabine and dasatinib. The polymer is encapsulated by nucleic acid aptamers that target the PDAC stromal microenvironment and shield the surface. The aptamer is removed upon arrival at the PDAC hypoxic microenvironment, exposing the positively charged core to achieve charge reversal. Particle size transformation is achieved using linkers that respond to a hypoxic microenvironment. Increased intratumoral penetration is achieved using the dual transformation capabilities of the formulation. Pairing these two agents can result in a powerful efficacy in chemotherapy sensitization and immune infiltration.

关键词： charge reversal chemosensitization immune infiltration pancreatic ductal adenocarcinoma size reduction

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Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead

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ADVANCED MATERIALS 2024年第11期36卷 2309582-2309582页

作者： li, xuwen Sun, Tao Jiang, Chen Fudan Univ Sch Pharm Dept Pharmaceut Minist EducKey Lab Smart Drug Delivery Shanghai 201203 Peoples R China MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China

Cancer metabolism plays multifaceted roles in the initiation and progression of tumors, and interventions in metabolism are considered fundamental approaches for cancer control. Within the vast metabolic networks of tumors, there exist numerous potential therapeutic targets, intricately interconnected with each other and with signaling networks related to immunity, metastasis, drug resistance, and more. Based on the characteristics of the tumor microenvironment, constructing drug delivery systems for multi-level modulation of the tumor microenvironment is proven as an effective strategy for achieving multidimensional control of cancer. Consequently, this article summarizes several features of tumor metabolism to provide insights into recent advancements in intelligent drug delivery systems for achieving multi-level regulation of the metabolic microenvironment in cancer, with the aim of offering a novel paradigm for cancer treatment. Latest advancements in intelligent drug delivery systems (DDS) exhibit distinctive advantages, including precise sensing, programmability, feedback control, and intrinsic activity. These attributes render them conducive to facilitating multi-dimensional therapeutic approaches grounded in metabolic ***

关键词： intelligent delivery systems metabolism regulation nanomedicine tumor metabolism

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Metabolic Nanoregulators Induce Ferroptosis and Change Metabolite Flow to Reverse Immunosuppressive Tumor Microenvironment

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ACS NANO 2024年第51期18卷 34996-35012页

作者： Wang, Yu Chen, Qinjun Luo, Yifan Qu, Yangqi li, xuwen Song, Haolin li, Chufeng Zhang, Yiwen Sun, Tao Jiang, Chen Fudan Univ Key Lab Smart Drug Delivery State Key Lab Med Neurobiol Dept PharmaceutSch PharmInst Brain SciMinist Ed Shanghai 201203 Peoples R China MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China Fujian Med Univ Affiliated Hosp 1 Natl Reg Med Ctr Dept Digest Dis Binhai Campus Fuzhou 350212 Peoples R China

Aberrant energy and substance metabolic pathways of tumor cells critically support tumor cell proliferation by hijacking the resources from nonmalignant cells, thereby establishing a metabolite flow favorable to tumor progression. This metabolic adaptation of tumor cells further modulates the immune landscape, ultimately creating a tumor microenvironment characterized by drug resistance and immunosuppression. The synergistic regulation of energy and substance metabolic pathways might be a good antitumor therapeutic paradigm. However, due to the metabolic convergence, it is crucial to selectively modulate the aberrant metabolism of tumor cells without compromising the functionality of other cells. Small-molecule drugs have the ability to target a wide range of biomolecules for antitumor therapy, but their application is limited by undesirable toxicities. Constructing nanodrug delivery systems can improve their properties and allow for the inclusion of multiple drugs, thereby exerting synergistic antitumor effects. In this study, we developed a two-drug codelivery system using drugs-conjugated multibranched polymers to modulate tumor cell metabolism by exploiting synthetic lethal pathways for safe and effective antitumor therapy. By delivery of adapalene and erastin simultaneously through nanoparticles, the material and energy metabolism of tumor cells can be regulated. This nanoparticle construction achieves tumor tissue targeting and responsive drug release, alters metabolite flow within tumor cells, and effectively kills tumor cells. Additionally, the nanoparticles can reverse the tumor immunosuppressive microenvironment, starting from single-cell regulation to whole-lesion control.

关键词： metabolic nanoregulators metabolite flow ferroptosis immunosuppression multibranched polymers

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A review: The structures and bioactivities of steroidal saponins from Allium macrostemon Bulbus

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PHYTOCHEMISTRY LETTERS 2023年第1期57卷 210-226页

作者： Xie, Huili Shi, Xiaolei Zhao, Dexin Wang, Bingzi Jin, Yongri li, xuwen Jilin Univ Coll Chem 2519 Jiefang Rd Changchun 130021 Peoples R China Jilin Univ Coll Food Sci & Engn Changchun 130062 Peoples R China

Allium macrostemon Bulbus (Xiebai in Chinese), as an important medicinal and edible homologous plant, has two kinds of original plants (the dry bulbs of Allium macrostemon and Allium chinense). In China, the dry bulbs of Allium macrostemon and Allium chinense have been used to treat some diseases for thousands of years. Steroidal saponins are considered to be one type of their most important active ingredients and research into the phar-macological activities of these compounds are currently undertaken. Some steroidal saponins may be promising therapeutic tools, which has caught the attention of researchers. This article provides a comprehensive overview of 102 steroidal saponins and sapogenins found in Allium macrostemon Bulbus, along with their reported phar-macological activities, including anti-inflammatory, antioxidant, antiplatelet aggregation, blood lipid-lowering, antitumor, and other beneficial effects. In this review, the extraction and isolation, spectral characteristics and pharmacological activities of steroidal saponins have been summarized based on literature from 1989 to 2022.

关键词： Allium macrostemon Bulbus Allium macrostemon Allium chinense Steroidal Saponins Chemical structure Bioactivity

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Sex differences in externalizing and internalizing traits and ventral striatal responses to monetary loss

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JOURNAL OF PSYCHIATRIC RESEARCH 2023年第1期162卷 11-20页

作者： li, Guangfei li, Yashuang Zhang, Zhao Chen, Yu li, Bao Hao, Dongmei Yang, lin Yang, Yimin li, xuwen li, Chiang-Shan R. Beijing Univ Technol Fac Environm & Life Dept Biomed Engn Beijing Peoples R China Beijing Int Sci & Technol Cooperat Base Intelligen Beijing Peoples R China Beijing Inst Technol Sch Life Sci Dept Biomed Engn Beijing Peoples R China Yale Univ Sch Med Dept Psychiat New Haven CT USA Yale Univ Sch Med Dept Neurosci New Haven CT USA Yale Univ Sch Med Interdept Neurosci Program New Haven CT USA Yale Univ Wu Tsai Inst New Haven CT USA Beijing Univ Technol 220 Life Sci Bldg 100 Pingleyuan Beijing 100124 Peoples R China Connecticut Mental Hlth Ctr S112 34 Pk St New Haven CT 06519 USA

Ventral striatum (VS) processes rewarding and punishing stimuli. Women and men vary in externalizing and internalizing traits, which may influence neural responses to reward and punishment. To investigate sex dif-ferences in how individual traits influence VS responses to reward and punishment, we curated the data of the Human Connectome Project and identified 981 (473 men) subjects evaluated by the Achenbach Adult Self-Report Syndrome Scales. We processed the imaging data with published routines and extracted VS response (beta) to win and to loss vs. baseline in a gambling task for correlation with externalizing and internalizing symptom severity. Men vs. women showed more severe externalizing symptoms and higher VS response to monetary losses (VS-loss beta) but not to wins. Men but not women showed a significant, positive correlation between VS-loss beta and externalizing traits, and the sex difference was confirmed by a slope test. The correlations of VS-loss vs. exter-nalizing and of VS-win vs. externalizing and those of VS-loss vs. externalizing and of VS-loss vs. internalizing traits both differed significantly in slope, confirming its specificity, in men. Further, the sex-specific relationship between VS-loss beta and externalizing trait did not extend to activities during exposure to negative emotion in the face matching task. To conclude, VS responses to loss but not to win and their correlation with externalizing rather than internalizing symptom severity showed sex differences in young adults. The findings highlight the relationship of externalizing traits and VS response to monetary loss and may have implications for psychological models of externalizing behaviors in men.

关键词： Externalizing VS Punishment Sex differences fMRI

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Synergistic optimization strategies for the development of multienzymatic cascade system-based electrochemical biosensors with enhanced performance

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BIOSENSORS & BIOELECTRONICS 2025年 274卷 117222页

作者： Zhu, Yuzhuo Cheng, Zhaoming Wang, Xueqi Zhang, Chuanjun li, xuwen Wei, Yanxue Wang, Jiajia Fang, Yuxin Wang, Yi Zhang, Di Tianjin Univ Tradit Chinese Med Coll Pharmaceut Engn Tradit Chinese Med Tianjin 301617 Peoples R China Tianjin Univ Tradit Chinese Med Inst Tradit Chinese Med Tianjin 301617 Peoples R China Tianjin Key Lab Intelligent & Green Pharmaceut Tra Tianjin 301617 Peoples R China State Key Lab Chinese Med Modernizat Tianjin 301617 Peoples R China Tianjin Univ Tradit Chinese Med Coll Acumox & Tuina Res Ctr Expt Acupuncture Sci Tianjin 301617 Peoples R China Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu Tianjin 301617 Peoples R China

Multienzymatic cascade system (MCS) strategies have been a topic of growing interest in the electrochemical biosensor research field owing to their many advantages. By combining two or more enzymes in an appropriate manner, MCS approaches can extend the range of detection for particular analytes while improving the overall efficiency of biocatalytic cascade reactions. Compared with mono-enzyme biosensors, the integration of MCS and electrochemical biosensor platforms is inherently more challenging owing to the increased complexity of the resultant system. In recent years, substantial progress in the development of MCS-based electrochemical biosensors with enhanced analytical performance has been made. This review provides an overview of the types of MCS strategies and their biosensor applications, together with a summary of synergistic optimization approaches that can help improve key parameters including sensitivity, selectivity, and stability when designing MCS-based electrochemical biosensors. These discussions include examples of published biosensor platforms (2016-2024) while also surveying key advances in associated research areas including redox mediators/enzyme coimmobilization, enzyme engineering, multienzyme spatial regulation, enzyme-nanozyme integration and others. Lastly, a brief overview of current challenges and future perspectives pertaining to MCS-based electrochemical biosensor design is provided.

关键词： Multienzymatic system Electrochemical biosensor Cascade reaction Synergistic strategy Enzymatic biosensor

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Reprogramming multi-stable snapping and energy dissipation in origami metamaterials through panel confinement

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PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES 2024年第2283期382卷 20240005页

作者： Almessabi, Abdulrahman li, xuwen Jamalimehr, Amin Pasini, Damiano McGill Univ Dept Mech Engn Montreal PQ H3A 0G4 Canada

With a focus on a class of origami-inspired metamaterials, this work explores the role of panel confinement in their mechanical response under cyclic loading. The goal is twofold: (i) quantify the magnitude change in snapping force and energy dissipation attained by varying the severity of confinement of selected panels;and (ii) leverage insights to modulate in situ their mechanical response as dictated by a given application, hence propose panel confinement modulation as a practical design route for response reprogrammability. Through computational modelling, proof-of-concept fabrication and cyclic testing, we first identify and characterize the governing factors enabling either the alteration or the preservation of the snapping force magnitude during repeated cycles of forward and backward loading. Then, we demonstrate how the in situ modulation of the constrained distance between selected panels enables reprogramming their snapping sequence and energy dissipation. The results contribute to expanding the versatility and application of this class of origami metamaterial across sectors, from aerospace to protective equipment, requiring precise control of mechanical damping and energy *** article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

关键词： origami metamaterials multi-stability energy dissipation reprogrammability

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Anti-rotation GNSS signal tracking algorithm based on symmetric dual antennas 22

Anti-rotation GNSS signal tracking algorithm based on symmet...

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8th International Conference on Computing and Artificial Intelligence, ICCAI 2022

作者： Zhang, Haidong li, xuwen Wu, Qiang Beijing University of Technology Information Department Beijing China

ISBN: (纸本)9781450396110

Due to periodic occlusion caused by rotating vehicles, the antenna cannot continuously receive GNSS signal. At the same time, the Doppler frequency shift caused by rotation also brings additional influence on GNSS signal tracking by the vehicles. This paper proposes a GNSS signal tracking algorithm based on dual antennas. The algorithm realizes the continuous and stable tracking of GNSS signal by signal preprocessing of symmetric dual antenna and joint calculation. Simulation results show that the algorithm can effectively reduce the influence of rotation on GNSS tracking PLL and improve the stability of tracking process. © 2022 ACM.

关键词： Rotation

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Nanomaterials with dual immunomodulatory functions for synergistic therapy of breast cancer brain metastases

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Bioactive Materials 2023年第9期27卷 474-487页

作者： Zhenhao Zhao Chufeng li Yiwen Zhang Chao li Yongchao Chu xuwen li Peixin liu Hongyi Chen Yu Wang Boyu Su Qinjun Chen Tao Sun Chen Jiang Department of Pharmaceutics School of PharmacyFudan UniversityKey Laboratory of Smart Drug DeliveryMinistry of EducationState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceShanghai201203China

A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain *** has made progress in the treatment of tumors,but limited by the non-immunogenicity of tumors and strong immunosuppressive environment,patients with TNBC brain metastases have not yet benefited from *** immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for ***,we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials(SIL@T).SIL@T modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells,releasing silybin and oxaliplatin responsively in the ***@T preferentially accumulates at the metastatic site and can significantly prolong the survival period of model *** studies have shown that SIL@T can effectively induce immunogenic cell death of metastatic cells,activate immune responses and increase infiltration of CD8+T ***,the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is *** study demonstrates that SIL@T with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.

关键词： Breast cancer brain metastases Drug delivery Immunogenic cell death Microenvironmental regulation STAT3

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Targeting Hypoxia and Autophagy Inhibition via Delivering Sonodynamic Nanoparticles With HIF-2α Inhibitor for Enhancing Immunotherapy in Renal Cell Carcinoma

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ADVANCED HEALTHCARE MATERIALS 2024年第32期13卷 e2402973页

作者： Zhu, Yihao li, Yajian li, xuwen Yu, Yuan Zhang, lingpu Zhang, Hanchen Chen, Can Chen, Dong Wang, Mingshuai Xing, Nianzeng Yang, Feiya Wasilijiang, Wahafu Ye, Xiongjun Chinese Acad Med Sci & Peking Union Med Coll Dept Urol Natl Canc Ctr Natl Clin Res Ctr CancCanc Hosp Beijing 100021 Peoples R China Chinese Acad Sci Hangzhou Inst Med Zhejiang Canc Hosp Hangzhou 310022 Zhejiang Peoples R China Chinese Acad Sci Inst Chem Lab Polymer Phys & Chem Beijing Natl Lab Mol Sci Beijing 100190 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Zunyi Med Univ Affiliated Hosp 2 Dept Oncol Zunyi 563000 Guizhou Peoples R China Shanxi Med Univ Canc Hosp Dept Urol Shanxi Prov Canc HospShanxi HospCanc HospChine Xian 030013 Shanxi Peoples R China

Immune checkpoint blockers (ICBs) therapy stands as the first-line treatment option for advanced renal cell carcinoma (RCC). However, its effectiveness is hindered by the immunosuppressive tumor microenvironment (TME). Sonodynamic therapy (SDT) generates tumor cell fragments that can prime the host's antitumor immunity. Nevertheless, the hypoxic microenvironment and upregulated autophagy following SDT often lead to cancer cell resistance. In response to these challenges, a hypoxia-responsive polymer (Poly(4,4 '-azobisbenzenemethanol-PMDA)-mPEG(5k), P-APm) encapsulating both a HIF-2 alpha inhibitor (belzutifan) and the ultrasonic sensitize (Chlorin e6, Ce6) is designed, to create the nanoparticle APm/Ce6/HIF. APm/Ce6/HIF combined with ultrasound (US) significantly suppresses tumor growth and activates antitumor immunity in vivo. Moreover, this treatment effectively transforms the immunosuppressive microenvironment from "immune-cold" to "immune-hot", thereby enhancing the response to ICBs therapy. The findings indicate that APm/Ce6/HIF offers a synergistic approach combining targeted therapy with immunotherapy, providing new possibilities for treating RCC.

关键词： HIF-2 alpha immunotherapy renal cell carcinoma sonodynamic therapy

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