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Acta Pharmaceutica Sinica B 2024年第2期14卷 897-899页

作者： Zekun Li Yongchun Pan Shiyu Du Yayao Li Chao Chen Hongxiu song Yueyao Wu Xiaowei Luan Qin Xu Xiaoxiang Guan yujun song Xin Han Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Medicine&Holistic Integrative MedicineJiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative MedicineNanjing University of Chinese MedicineNanjing 210023China College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional MaterialsState Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

The authors regret that there is an error in the article Fig.5E due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading.Although it does not affect the conclusion,it is an obvious error.The authors have now modified as below.The authors apologize for any inconvenience caused to the journal and readers.

关键词： journal correction conclusion

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 795-807页

作者： Yongchun Pan Xiaowei Luan Fei Zeng Xuyuan Wang Shurong Qin Qianglan Lu Guanzhong He Yanfeng Gao Xiaolian Sun Xin Han Bangshun He yujun song Department of Laboratory Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China State Key Laboratory of Natural Medicines Key Laboratory of Drug Quality Control and PharmacovigilanceDepartment of Pharmaceutical AnalysisChina Pharmaceutical UniversityNanjing 211198China School of Medicine&Holistic Integrative Medicine Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression.Here,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer therapy.In this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are packaged.To intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as well.When the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells.These tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation therapy.Overall,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

关键词： CRISPRdelivery Enzymeencapsulation Logic gate Hybridmaterial Hypoxia Gene editing Precise nanomedicine Multimodal therapy

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

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Nano Research 2024年第3期17卷 1748-1759页

作者： Zhenxing Zhu Dongtao Zhou Yi Yin Zhun Li Zhen Guo Yongchun Pan Yanfeng Gao Jingjing Yang Weiming Zhu yujun song Yi Li Department of General Surgery Affiliated Jinling HospitalMedical SchoolNanjing UniversityNanjing 210093China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Department of General Surgery Affiliated Drum Tower HospitalMedical SchoolNanjing UniversityNanjing 210008China Department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineJiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Inflammatory bowel disease(IBD)is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the intestine.Excessive pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in IBD.Here,we designed an oral pyroptosis nanoinhibitor,DXMS@CuM@PPADT@PSS(DCMP),which can target intestinal lesions,and respond to reactive oxygen species(ROS)to release active sites and drugs at the lesion.DCMP can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3(NLRP3)inflammasomes by scavenging ROS,resulting in the down-regulation of gasdermin D(GSDMD)cleavage thus inhibiting pyroptosis.It also improved intestinal barrier function,decreased inflammatory cytokine levels,and increased the diversity of gut microbiota in mice with colitis.This work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

关键词： inflammatory bowel disease nanoinhibitors pyroptosis synergistic therapy antioxidant

Solid-phase sintering and vapor-liquid-solid growth of BP@MgO quantum dot crystals with a high piezoelectric response

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Journal of Advanced Ceramics 2022年第11期11卷 1725-1734页

作者： Qingwei LIAO Wei HOU Kexuan LIAO Liyin CHEN yujun song Guowei GAO Lei QIN Key Laboratory of Sensors Beijing Information Science&Technology UniversityBeijing 100192China Key Laboratory of Modern Measurement&Control Technology Ministry of EducationBeijing Information Science&Technology UniversityBeijing 100192China Key Laboratory of Photoelectric Testing Technology Beijing Information Science&Technology UniversityBeijing 100192China School of Chemical Science and Engineering Tongji UniversityShanghai 200092China Harvard John A.Paulson School of Engineering and Applied Sciences Harvard UniversityCambridge 02138USA Center of Modern Physics Technology School of Mathematics and PhysicsUniversity of Science and Technology BeijingBeijing 100083China

Low-dimensional piezoelectric and quantum piezotronics are two important branches of low-dimensional materials,playing a significant role in the advancement of low-dimensional devices,circuits,and systems.Here,we firstly propose a solid-phase sintering and vapor–liquid–solid growth(SS–VLS-like)method of preparing a quantum-sized oxide material,i.e.,black phosphorus(BP)@MgO quantum dot(QD)crystal with a strong piezoelectric response.Quantum-sized MgO was obtained by Mg slowly released from MgB_(2) within the confinement of a nanoflake BP matrix.Since the slow release of Mg only grows nanometer-sized MgO to hinder the further growth of MgO,we added a heterostructure matrix constraint:nanoflake BP.With the BP as the matrix confinement,MgO QDs embedded in the BP@MgO QD crystals were formed.These crystals have a layered two-dimensional(2D)structure with a thickness of 11 nm and are stable in the air.In addition,piezoresponse force microscopy(PFM)images show that they have extremely strong polarity.The strong polarity can also be proved by polarization reversal and a simple pressure sensor.

关键词： quantum dots(QDs) piezoelectric black phosphorus(BP) MgO

Emerging trends in organ-on-a-chip systems for drug screening

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药学学报:英文版 2023年第6期13卷 2483-2509页

作者： Yanping Wang Yanfeng Gao Yongchun Pan Dongtao Zhou Yuta Liu Yi Yin Jingjing Yang Yuzhen Wang yujun song College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Sino-French Engineer School Nanjing University of Science and TechnologyNanjing 210094China Key Laboratory of Flexible Electronics&Institute of Advanced Materials Jiangsu National Synergistic Innovation Center for Advanced MaterialsNanjing Tech UniversityNanjing 211816China

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall,this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

关键词： Microfluidics Drug discovery In vitro models Microphysiological systems Toxicity assessment Bioprinting Drug safety Human-on-a-chip

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4224-4234页

作者： Zekun Li Yongchun Pan Shiyu Du Yayao Li Chao Chen Hongxiu song Yueyao Wu Xiaowei Luan Qin Xu Xiaoxiang Guan yujun song Xin Han Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Medicine&Holistic Integrative MedicineJiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative MedicineNanjing University of Chinese MedicineNanjing 210023China College of Engineering and Applied Sciences Jiangsu Key Laboratory of Artificial Functional MaterialsState Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNajing 210023China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

Near-infrared(NIR)-light-triggered nanomedicine, including photodynamic therapy(PDT)and photothermal therapy(PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania(TiO_(2-x)) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase(HAase) and glutathione(GSH) can readily destroy hyaluronic acid(HA) and disulfide bond and releases the Cas9/sgRNA from TiO_(2-x) to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2(NRF2) and heat shock protein 90a(HSP90a), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_(2-x) demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

关键词： Near infrared phototherapy Gene editing Nuclear factor E2-related factor 2 .Heat shock protein 90c TiO_(2-x) Sensitized phototherapy Nanoprodrug Tumor microenvironment

Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2176-2187页

作者： Chuan Hu yujun song Yiwei Zhang Siqin He Xueying Liu Xiaotong Yang Tao Gong Yuan Huang Huile Gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy.Herein,a kind of tumor cascade-targeted responsive liposome(NLG919@Lip-pep1)is developed by conjugating polypeptide inhibitor of PD-1 signal pathway(AUNP-12),which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2(MMP-2)cleavable peptide(GPLGVRGD).This targeted liposome is prepared through a mature preparation process,and indoleamine-2,3-dioxygenase(IDO)inhibitor NLG919 was encapsulated into it.Moreover,mediated by the enhanced permeability and retention effect(EPR effect)and AUNP-12,NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues.At the same time,the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12,thus realizing the precise block of PD-1 signal pathway,and restoring the activity of T cells.The exposure of secondary targeting moduleⅡVRGDC-NLG919@Lip mediated tumor cells targeting,and further relieved the immunosuppressive microenvironment.Overall,this study offers a potentially appealing paradigm of a high efficiency,low toxicity,and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer,which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

关键词： Immunotherapy Cascade targeting Liposome MMP-2 responsive Breast cancer ICBs IDO inhibitors Immunosuppressive microenvironment

Recent advances of microneedles for biomedical applications: drug delivery and beyond

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Acta Pharmaceutica Sinica B 2019年第3期9卷 469-483页

作者： Jian Yang Xinli Liu Yunzhi Fu yujun song College of Materials Science and Chemical Engineering Hainan UniversityHaikou570228China College of Engineering and Applied Sciences Nanjing UniversityNanjing210093China

The microneedle(MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing(3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.

关键词： Microneedle patches Biomedical applications Microfabricated device Drug delivery Disease treatment Disease diagnosis Immunobiological administration 3D printing

Shell-driven Fine Structure Transition of Core Materials in Co@Au Core-shell Nanoparticles

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Nano-Micro Letters 2012年第4期4卷 235-242页

作者： yujun song Yinghui Wang Shaoxia Ji Jie Ding School of Materials Science and Engineering Beihang University

Co@Au core shell nanoparticles(NPs) of different shell thicknesses were fabricated by a combination of the displacement process and the reduction-deposition process in a microfluidic reactor. The effect of the shell thickness on the fine structures(local atom arrangement) of core materials was investigated by X-ray Absorption Near Edge Structure(XANES) and Extended X-ray Absorption Fine Structure(EXAFS).The results indicate that the shell thickness affects the fine structure of the core materials by causing atomic re-arrangement between the hexagonal close pack(hcp) and the face centered cubic(fcc) structure, and forming Co-Au bonds in the core-shell interface.

关键词： Nanoparticle Core-shell Fine Structure Microfluidic

Highly biocompatible BSA-MnO_2 nanoparticles as an efficient near-infrared photothermal agent for cancer therapy

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Chinese Chemical Letters 2018年第11期29卷 1685-1688页

作者： Yuzhen Wang yujun song Guixian Zhu Dechen Zhang Xuewu Liu Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM) Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM)Nanjing Tech University (NanjingTech) Department of Biomedical Engineering College of Engineering and Applied SciencesNanjing University Department of Nanomedicine Houston Methodist Research Institute

More recently, the biomedical applications of MnO2 in bioanalysis, cell imaging, and drug delivery as a result of their appealing physicochemical properties, have been reported and expanded rapidly. However, research on a near infrared （NIR） photothermal response of MnO2 was ignored. In this work, we reported a facile, one-pot method to synthesis of bovine serum albumin （BSA）-reduced and stabilized MnO2 nanoparticles （BSA-MnO2 NPs） with good aqueous dispersibility and high biocompatibility. And we also showed for the first time that BSA-MnO2 NPs displayed superior NIR photothermal efficiency and photostability which demonstrated as a novel class of photothermal antitumor agent.

关键词： Bovine serum albumin Manganese dioxide Photothermal NIR Cancer therapy