Yukun Duan
Email Address
cheduan@nus.edu.sg
31 results
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Publication Light-Induced Self-Escape of Spherical Nucleic Acid from Endo/Lysosome for Efficient Non-Cationic Gene Delivery(WILEY-V C H VERLAG GMBH, 2020) Shi, Leilei; Wu, Wenbo; Duan, Yukun; Xu, Li; Xu, Yingying; Hou, Lidan; Meng, Xiangjun; Zhu, Xinyuan; Liu, Bin; Prof Bin Liu; MATERIALS SCIENCE AND ENGINEERING; CHEMICAL & BIOMOLECULAR ENGINEERINGDeveloping non-cationic gene carriers and achieving efficient endo/lysosome escape of functional nucleic acids in cytosol are two major challenges faced by the field of gene delivery. Herein, we demonstrate the concept of self-escape spherical nucleic acid (SNA) to achieve light controlled non-cationic gene delivery with sufficient endo/lysosome escape capacity. In this system, Bcl-2 antisense oligonucleotides (OSAs) were conjugated onto the surface of aggregation-induced emission (AIE) photosensitizer (PS) nanoparticles to form core–shell SNA. Once the SNAs were taken up by tumor cells, and upon light irradiation, the accumulative O produced by the AIE PSs ruptured the lysosome structure to promote OSA escape. Prominent in vitro and in vivo results revealed that the AIE-based core–shell SNA could downregulate the anti-apoptosis protein (Bcl-2) and induce tumor cell apoptosis without any transfection reagent. 1 2Publication Precise Molecular Design for High-Performance Luminogens with Aggregation-Induced Emission(Wiley, 2020-01-01) Xu, S; Duan, Y; Liu, B; Mr Duan Yukun; CHEMICAL & BIOMOLECULAR ENGINEERING© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Precise design of fluorescent molecules with desired properties has enabled the rapid development of many research fields. Among the different types of optically active materials, luminogens with aggregation-induced emission (AIEgens) have attracted significant interest over the past two decades. The negligible luminescence of AIEgens as a molecular species and high brightness in aggregate states distinguish them from conventional fluorescent dyes, which has galvanized efforts to bring AIEgens to a wide array of multidisciplinary applications. Herein, the useful principles and emerging structure–property relationships for precise molecular design toward AIEgens with desirable properties using concrete examples are revealed. The cutting-edge applications of AIEgens and their excellent performance in enabling new research directions in biomedical theranostics, optoelectronic devices, stimuli-responsive smart materials, and visualization of physical processes are also highlighted.Publication Color-Tunable Light-up Bioorthogonal Probes for In Vivo Two-Photon Fluorescence Imaging(Wiley, 2020-04-06) Dou, Y; Wang, Y; Duan, Y; Liu, B; Hu, Q; Shen, W; Sun, H; Zhu, Q; Mr Duan Yukun; CHEMICAL & BIOMOLECULAR ENGINEERING© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Light-up bioorthogonal probes have attracted increasing attention recently due to their capability to directly image diverse biomolecules in living cells without washing steps. The development of bioorthogonal probes with excellent fluorescent properties suitable for in vivo imaging, such as long excitation/emission wavelength, high fluorescence turn-on ratio, and deep penetration, has been rarely reported. Herein, a series of azide-based light-up bioorthogonal probes with tunable colors based on a weak fluorescent 8-aminoquinoline (AQ) scaffold were designed and synthesized. The azido quinoline derivatives are able to induce large fluorescence enhancement (up to 1352-fold) after click reaction with alkynes. In addition, the probes could be engineered to exhibit excellent two-photon properties (δ=542 GM at 780 nm) after further introducing different styryl groups into the AQ scaffold. Subsequent detailed bioimaging experiments demonstrated that these versatile probes can be successfully used for live cell/zebrafish imaging without washing steps. Further in vivo two-photon imaging experiments demonstrated that these light-up biorthogonal probe outperformed conventional fluorophores, for example, high signal-to-noise ratio and deep tissue penetration. The design strategy reported in this study is a useful approach to realize diverse high-performance biorthogonal light-up probes for in vivo studying.Publication Activation of Pyroptosis by Membrane‐Anchoring AIE Photosensitizer Design: New Prospect for Photodynamic Cancer Cell Ablation(Wiley, 2021) Wu, Min; Liu, Xingang; Chen, Huan; Duan, Yukun; Liu, Jingjing; Pan, Yutong; Liu, Bin; Prof Bin Liu; CHEMICAL & BIOMOLECULAR ENGINEERINGPyroptosis as a lytic and inflammatory form of cell death is a powerful tool to fight against cancer. However, pyroptosis is usually activated by chemotherapeutic drugs, which limits its anti-tumor applications due to drug resistance and severe side effects. Herein, we demonstrate that membrane targeting photosensitizers can induce pyroptosis for cancer cell ablation with noninvasiveness and low side effects. A series of membrane anchoring photosensitizers (TBD-R PSs) with aggregation-induced emission (AIE) characteristics were prepared through conjugation of TBD and phenyl ring with cationic chains. Upon light irradiation, cytotoxic ROS were produced in situ, resulting in direct membrane damage and superior cancer cell ablation. Detailed study revealed that pyroptosis gradually became the dominant cell death pathway along with the increase of TBD-R PSs membrane anchoring capability. This study offers a photo-activated pyroptosis-based intervention strategy for cancer cell ablation.Publication Biomimetic Nanocomposites Cloaked with Bioorthogonally Labeled Glioblastoma Cell Membrane for Targeted Multimodal Imaging of Brain Tumors(Wiley, 2020-01-01) Duan, Y; Wu, M; Hu, D; Pan, Y; Hu, F; Liu, X; Thakor, N; Ng, WH; Liu, X; Sheng, Z; Zheng, H; Liu, B; Mr Yukun Duan; ELECTRICAL AND COMPUTER ENGINEERING; DUKE-NUS MEDICAL SCHOOL; NUS NANOSCIENCE & NANOTECH INITIATIVE; CHEMICAL & BIOMOLECULAR ENGINEERING© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Brain tumor targeted delivery of diagnostic contrast agents has been an elusive goal due to the presence of the blood brain barrier (BBB) and the complex brain tumor microenvironment. Herein, an ingenious design of nanoscale contrast agents coated by bioorthogonally labeled brain tumor cell membrane for targeted diagnosis of glioblastoma through multiple complementary imaging modalities is presented. Taking advantage of bioorthogonal click reactions, an endothelial integrin receptor-targeting peptide cRGD is decorated onto the nanocomposite surface to act in synergy with brain tumor cell membrane to offer BBB-penetrating and homotypic targeting effect in the brain tumor microenvironment. Cellular and animal experimental results validate the superior targeting outcomes achieved by cRGD-labeled brain tumor cell membrane coating. This study offers an example of a surface modified cell membrane as a potential theranostic strategy to overcome the delivery barriers in brain tumors.Publication Precise Molecular Engineering of Photosensitizers with Aggregation-Induced Emission over 800 nm for Photodynamic Therapy(WILEY-VCH VERLAG, 2019-08-28) Wu, Wenbo; Mao, Duo; Xu, Shidang; Panahandeh-Fard, Majid; Duan, Yukun; Hu, Fang; Kong, Deling; Liu, Bin; Mr Duan Yukun; MATERIALS SCIENCE AND ENGINEERING; NUS NANOSCIENCE & NANOTECH INITIATIVE; CHEMICAL & BIOMOLECULAR ENGINEERING© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Owing to efficient singlet oxygen (1O2) generation in aggregate state, photosensitizers (PSs) with aggregation-induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high 1O2 generation efficiency, strong molar absorption in long-wavelength range and near-infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short-wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation-induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high 1O2 generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8, which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in 1O2 generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.Publication Organic molecules with propeller structures for efficient photoacoustic imaging and photothermal ablation of cancer cells(Royal Society of Chemistry (RSC), 2017-08-01) Cai, X; Liu, J; Liew, WH; Duan, Yukun; Geng, J; Thakor, N; Yao, K; Liao, LD; Liu, B; Mr Duan Yukun; ELECTRICAL AND COMPUTER ENGINEERING; LIFE SCIENCES INSTITUTE; MECHANICAL ENGINEERING; CHEMICAL & BIOMOLECULAR ENGINEERING© 2017 the Partner Organisations. Photoacoustic (PA) imaging has recently attracted great attention due to its noninvasive and nonionizing properties and high penetration depth. This technique is particularly attractive for sentinel lymph node (SLN) imaging, which is highly desirable during sentinel lymph node biopsy for the detection of breast cancer metastasis. In this work, we report the design and synthesis of BTPETTQ with a propeller structure and a donor-acceptor-donor configuration, which exhibits strong NIR absorption, extremely weak fluorescence and a high PA signal in solution as molecular species. After being encapsulated into a polymeric matrix, BTPETTQ nanoparticles (NPs) also show excellent PA signal output, which is superior to the widely used gold nanorods based on the same mass and is also better than that from the NPs based on the core molecule of TTQ without tetraphenylethene modification. High-resolution PA imaging of SLN is achieved after injection of BTPETTQ NPs into the left paw of rats. The good photothermal conversion efficiency (40%) of BTPETTQ NPs also ensures their good performance in photothermal therapy, which is validated by the effective killing of HeLa cells upon 808 nm laser irradiation. This work demonstrates the great potential of compounds with propeller structures for PA imaging and photothermal therapy applications.Publication Biodegradable Nanoscale Coordination Polymers for Targeted Tumor Combination Therapy with Oxidative Stress Amplification(WILEY-VCH VERLAG, 2020-02-12) Liu, Jingjing; Wu, Min; Pan, Yutong; Duan, Yukun; Dong, Ziliang; Chao, Yu; Liu, Zhuang; Liu, Bin; Dr Liu Jingjing; CHEMICAL & BIOMOLECULAR ENGINEERING© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Nowadays various inorganic nanoparticles that generate highly reactive hydroxyl radical (·OH) on the basis of Fenton-like catalytic activity of metal ions have been designed for chemodynamic therapy. However, the high level of adaptive antioxidants [glutathione (GSH)] in cancer cells could effectively consume ·OH to compromise the treatment efficiency and biosafety of these inorganic nanoparticles, and this is a general concern in chemodynamic therapy. Herein, a new biodegradable nanoscale coordination polymer (NCP) is developed by integration of cisplatin prodrug (DSCP) and iron (III) ions through a reverse microemulsion method. The DSCP in the NCPs could react with GSH to release free cisplatin, while the iron (III) ions could be reduced by GSH into iron (II) to enable Fenton reaction, subsequently leading to amplified intracellular oxidative stress. After surface modification of polyethylene glycol (PEG) and cyclo[Arg-Gly-Asp-D-Phe-Lys(mpa)] peptide (cRGD), Fe-DSCP-PEG-cRGD shows an excellent targeting effect against αvβ3-integrin overexpressed tumor cells. Furthermore, Fe-DSCP-PEG-cRGD enables significant chemo and chemodynamic therapy with dramatically enhanced therapeutic efficiency in comparison to relative monotherapies. Importantly, Fe-DSCP-PEG-cRGD could be efficiently cleared out from mice through feces and urine postinjection 7 days. The NCP presented in this work is simple and economical, which shows great biodegradability and biosafety for potential clinical translation.Publication Recent advances of AIE dots in NIR imaging and phototherapy(Royal Society of Chemistry (RSC), 2019-11-07) Zhang, R; Duan, Y; Liu, B; Mr Duan Yukun; CHEMICAL & BIOMOLECULAR ENGINEERING© 2019 The Royal Society of Chemistry. Nanomaterials are indispensable tools for imaging and therapy. Organic dots with aggregation-induced emission characteristics (AIE dots) have emerged as a new nanolight for their ultra-brightness, excellent photostability and biocompatibility. Due to the rotor structures, most of the reported AIE luminogens show short wavelength absorption and emission, an intrinsic disadvantage for their biomedical applications. Recently, more exciting examples reveal that properly designed AIE dots can easily reach NIR emission, excitable by near-infrared (NIR) light via multiphoton processes, which also have great potentials in photoacoustic imaging (PAI) and phototherapy. In this review, we summarize the recent advances of AIE nanomaterials for NIR fluorescence imaging, PAI, image-guided photodynamic and photothermal therapy (PDT and PTT). We highlight various strategies to improve the energy conversion efficiency of AIE dots through controlling different energy decay pathways. With this review, we hope to encourage more precise design of organic nanomaterials for biomedical applications.Publication Direct Synthesis of Photosensitizable Bacterial Cellulose as Engineered Living Material for Skin Wound Repair(WILEY-V C H VERLAG GMBH, 2022-04) Liu, Xingang; Wu, Min; Wang, Meng; Hu, Qida; Liu, Jingjing; Duan, Yukun; Liu, Bin; Prof Bin Liu; CHEMICAL & BIOMOLECULAR ENGINEERINGLiving materials based on bacterial cellulose (BC) represent a natural and promising candidate for wound dressing. Both physical adsorption and chemical methods have been applied to BC for realizing antibacterial function. However, effective and long-lasting incorporation of bactericidal moieties to BC remains challenging. Herein, a Komagataeibacter sucrofermentans-based direct synthetic method to fabricate photosensitizer-grafted BC through in situ bacterial metabolism in the presence of TPEPy-modified glucose is explored. The results verify that the direct biosynthesis method is efficient and convenient to endow BC with outstanding fluorescence and light-triggered photodynamic bactericidal activity for skin wound repair. This work presents a new approach to fabricate eco-friendly and active wound dressing with light-controlled bactericidal activity by microbial metabolism. The successful modification of the glucose carbon source of microorganisms also offers insights for biosyntheses of other living materials through microbial metabolism.