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Manipulating the intramolecular motion of AIEgens for boosted biomedical applications

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Science China Chemistry 2019年第8期62卷 929-932页

作者： hanlin ou Shuxin Dai Ruihua Liu Dan Ding Key Laboratory of Bioactive Materials Ministry of EducationState Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai University

The research in the biomedical applications of aggregation? induced emission luminogens (AIEgens) has attracted increasing interest in recent years, as AIEgens have been widely accepted as promising materials for constructing new generation of phototheranostic agents [1-5]. Different from conventional organic dyes, the AIEgens often have threedimensional (3D) molecular structure and contain a number of intramolecular motion units [6-8]. In the aggregates, the 3D molecular structure results in significantly reduced intermolecular interaction such as π-π stacking as compared to planar structure.

关键词： Manipulating intramolecular biomedical applications

Gathering brings strength:How organic aggregates boost disease phototheranostics

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Aggregate

Aggregate 2021年第1期2卷 95-113页

作者： Ji Qi hanlin ou Qian Liu Dan Ding State Key Laboratory of Medicinal Chemical Biology Nankai UniversityTianjinChina Key Laboratory of Bioactive Materials Ministry of Educationand College of Life SciencesNankai UniversityTianjinChina Department of Urology Tianjin First Central HospitalTianjinChina

Phototheranostics that concurrently and complementarily integrate real-time diagnosis and in situ therapeutic capabilities in one platform has become the advancing edge of precision *** agents possess the merits of facile preparation,high purity,tunable photophysical property,good biocompatibility,and potential biodegradability,which have shown great promise for disease *** review summarizes the recent achievements of organic phototheranostic agents and applications,especially which rationally utilize energy dissipation pathways of Jablonski diagram to modulate the fluorescence emission,photoacoustic/photothermal production,and photodynamic *** particular interest are the systems exhibiting huge differences in aggregate state as compared with the solution or single molecule form,during which the intramolecular motions play an important role in regulating the photophysical *** recent advances from such an aspect for biomedical applications including high-resolution imaging,activatable imaging and therapy,adaptive theranostics,image-guided surgery,immunotherapy,and afterglow imaging are discussed.A brief summary and perspective in this field are also *** hope this review will be helpful to the researchers interested in bioprobe design and theranostic applications,and inspire new insights into the linkage between aggregate science and biomedical field.

关键词： activatable probe aggregate aggregation-induced emission intramolecular motion Jablonski diagram phototheranostics

Surface-adaptive nanoparticles with near-infrared aggregation-induced emission for image-guided tumor resection

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Science China(Life Sciences) 2019年第11期62卷 1472-1480页

作者： Xiaoyan Zhang Cong Li Wenyi Liu hanlin ou Dan Ding Key Laboratory of Bioactive Materials Ministry of EducationCollege of Life SciencesNankai UniversityTianjin 300071China Tianjin Stomatological Hospital Hospital of StomatologyMedical CollegeNankai UniversityTianjin 300041China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhou 221002China

Aggregation-induced emission(AIE)nanoparticles(NPs)are widely used for image-guided tumor resection because of their high signal-to-noise ratios and long systemic circulation *** NPs are derived by encapsulating small-molecule fluorescent dyes with AIE property inside the cores of NPs assembled by amphiphilic *** the systemic circulation of AIE NPs is prolonged,hydrophilic polymer coatings simultaneously decrease the binding and uptake of AIE NPs by tumor *** overcome this problem,surface-adaptive AIE dye-encapsulated mixed-shell micelles(MSMs)with polyethylene glycol/poly(β-amino ester)(PEG/PAE)surfaces were *** to the charge conversion ability of PAE,MSMs demonstrated enhanced cellular uptake by tumor cells in acidic *** addition,compared with single-PEG-shelled micelles(PEGSMs),MSMs exhibited prolonged systemic circulation due to the presence of micro-phase separated ***,due to the coordination effect of enhanced cancer cell uptake and prolonged systemic circulation time,MSMs were more enriched than PEGSMs in the tumor cells and exhibited excellent performance during image-guided tumor resection.

关键词： aggregation-induced emission surface-adaptive enhanced cellular uptake image-guided tumor resection

Largeπ-extended donor-acceptor polymers for highly efficient in vivo near-infrared photoacoustic imaging and photothermal tumor therapy

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Science China Chemistry 2021年第12期64卷 2180-2192页

作者： Jiangao Li hanlin ou Jing Li Xiaodi Yang Congwu Ge Dan Ding Xike Gao Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of EducationCollege of Life SciencesNankai UniversityTianjin300071China China Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese MedicineShanghai201203China

Semiconducting polymers(SPs)with intensive near-infrared(NIR)absorption and high photothermal conversion efficiencies have been employed as a new generation of photothermal agents(PTAs)for“all-in-one”theranostic nanoplatforms with integrated photoacoustic imaging(PAI)and photothermal therapy(PTT)***,the lack of facile molecular design principles impedes the development of highly efficient NIR ***,a facile molecular design strategy based on largeπ-extended donor-acceptor(L-π-D-A)structure is reported for achieving SPs(SP1-SP3)with highly efficient in vitro and in vivo PAI and PTT *** adjusting the conjugation length and planarity of the donor units,both SP3 and corresponding nanoparticle(SPN)SPN3 exhibit stronger D-A strength,intensive NIR absorption,enhanced absorption coefficient,and higher photothermal conversion efficiency(up to 61.8%).The excellent photothermal conversion efficiencies make SPN1-SPN3 produce efficient inhibition of tumor growth with excellent biocompatibility and prominent PAI performance with a high contrast manner in living mice at a low systemic injection *** research highlights that the new L-π-D-A molecular design is an effective strategy to obtain highly efficient polymeric NIR PTAs for high desirable cancer phototheranostic nanoplatforms.

关键词： D-A polymers near-infrared photothermal agents photoacoustic imaging photothermal therapy

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Sonosensitized Aggregation-Induced Emission Dots with Capacities of Immunogenic Cell Death Induction and Multivalent Blocking of Programmed Cell Death-Ligand 1 for Amplified Antitumor Immunotherapy

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CCS Chemistry 2022年第2期4卷 501-514页

作者： Shaorui Jia Zhiyuan Gao Zelin Wu Heqi Gao He Wang hanlin ou Dan Ding Key Laboratory of Bioactive Materials Ministry of Education College of Life SciencesState Key Laboratory of Medicinal Chemical BiologyNankai UniversityTianjin 300071 Department of Urology First Affiliated Hospital of Soochow UniversitySuzhou 215006

The combination of immunogenic cell death(ICD)induction and immune checkpoint blockade has emerged as a major direction of cancer *** currently available ICD inducers,sonosensitizers that produce reactive oxygen species(ROS)under an external trigger to evoke ICD of tumor cells have shown great ***,a highly efficient sonosensitizer-based ICD inducer with an aggregationinduced emission(AIE)characteristic has yet to be ***,a novel AIE sonosensitizer with a twisted molecular structure,very small energy gap between the singlet and triplet excited states(ΔE_(ST)),and efficient ROS generation ability,which can serve as an effective ICD inducer,is reported for sonodynamic processes in cancer ***,an AIE sonosensitizer-based nanosystem with surface modification of anti-PD-L1 peptide is constructed for boosting antitumor *** this system,AIE sonosensitizer-mediated sonodynamic therapy can successfully convert a hypoimmunogenic cold tumor to a hot one and further facilitate the multivalent blocking of programed death ligand(PD-L1)by anti-PD-L1 *** an advanced nanosystem could effectively initiate the activation of antitumoral immune reactions and modulation of an immunosuppressive microenvironment,contributing to systemic antitumor effects to further inhibit the growth of distant tumors.

关键词： aggregation-induced emission sonodynamic therapy immunogenic cell death PD-L1 antitumor immunotherapy

Organic/polymer photothermal nanoagents for photoacoustic imaging and photothermal therapy in vivo

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Science China Materials 2019年第11期62卷 1740-1758页

作者： hanlin ou Jun Li Chao Chen Heqi Gao Xue Xue Dan Ding Key Laboratory of Bioactive Materials Ministry of Educationand College of Life SciencesNankai UniversityTianjin 300071China State Key Laboratory of Medicinal Chemical Biology and College of PharmacyNankai UniversityTianjin 300353China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhou 221002China

In recent years,organic/polymer photothermal nanoagents including semiconducting polymer nanoparticles and small-molecule organic photothermal agents-encapsulated nanoparticles have attracted large attention from researchers in the biomedical field,owing to their excellent optical properties,good biocompatibility,easy processability,and flexible surface functionalization,as well as their combined functions of photoacoustic(PA)imaging and photothermal therapy(PTT).In this review,we summarize the recent advances in organic/polymer photothermal nanoagents for in vivo PA imaging and PTT *** particular,we focus on the design strategies,which are composed of traditional approaches and emerging mechanisms,especially based on'intramolecular motion-induced photothermy'strategy to regulate the photophysical properties of organic/polymer photothermal nanoagents for boosted in vivo PA imaging and PTT.

关键词： photothermal agent photoacoustic imaging photothermal therapy semiconducting polymer nanoparticle

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

Late Cenozoic Activity of the Tashkurgan Normal Fault and Implications for the Origin of the Kongur Shan Extensional System, Eastern Pamir

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Journal of Earth Science 2020年第4期31卷 723-734页

作者： Shenqiang Chen hanlin Chen School of Earth Sciences Zhejiang UniversityHangzhou 310027China Department of Earth Sciences ETH ZurichZurich 8092Switzerland

In the northwest of the Himalayan-Tibetan Orogen, the ~250 km-long Kongur Shan extensional system in the eastern Pamir was formed during the convergence between the Indian and Asian plates. Tectonic activity of the Kongur Shan normal fault and the Tashkurgan normal fault can help to reveal the origin of east-west extension along the Kongur Shan extensional system. The Kongur Shan fault has been extensively studied, while the Tashkurgan fault calls for systemic research. In this study, low-temperature thermochronology including apatite fission track analysis and apatite and zircon(U-Th)/He analyses is applied to constrain the timing of activity of the Tashkurgan fault. Results indicate that the Tashkurgan fault initiated at 10–5 Ma, and most likely at 6–5 Ma. The footwall of the Tashkurgan fault has been exhumed at an average exhumation rate of 0.6–0.9 mm/a since the initiation of the Tashkurgan fault. Combined with previous research on the Kongur Shan fault, we believe that the origin of east-west extension along the Kongur Shan extensional system was driven by gravitational collapse of over-thickened Pamir crust.

关键词： Pamir Late Cenozoic extension normal fault low-temperature thermochronology

Thickness dependence of viscoelastic stress relaxation of laminated microbeams due to mismatch strain

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Applied Mathematics and Mechanics(English Edition) 2022年第4期43卷 467-478页

作者： Xiaosheng CAI Nenghui ZHANG hanlin LIU Shanghai Institute of Applied Mathematics and Mechanics Shanghai Key Laboratory of Mechanics in Energy EngineeringSchool of Mechanics and Engineering ScienceShanghai UniversityShanghai 200072China

Time-dependent behaviors due to various mismatch strains are very important to the reliability of micro-/*** paper aims at presenting an analytical model to study the viscoelastic stress relaxation of the laminated microbeam caused by mismatch ***,Zhang’s two-variable method is used to establish a mechanical model for predicting the quasi-static stress relaxation of the laminated ***,the related analytical solutions are obtained by combining the differential method and the eigenvalue method in the temporal ***,the influence of the substrateto-film thickness/modulus ratio on the relaxation responses of the laminated microbeam subject to a step load of the mismatch strain is *** results show that the present predictions are consistent with the previous theoretical ***,the thickness dependence of stress relaxation time of the laminated microbeam is jointly determined by the intrinsic structural evolution factors and tension-bending coupling state;the stress relaxation time can be controlled by adjusting the substrate-to-film thickness/modulus ratio.

关键词： laminated structure stress relaxation mismatch strain tension-bending coupling effect analytical method