FNU Kenry

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• Dhoble, S., Wu, T. H., & Kenry, . (2024). Decoding Nanomaterial-Biosystem Interactions through Machine Learning. Angewandte Chemie (International ed. in English), 63(16), e202318380.
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  The interactions between biosystems and nanomaterials regulate most of their theranostic and nanomedicine applications. These nanomaterial-biosystem interactions are highly complex and influenced by a number of entangled factors, including but not limited to the physicochemical features of nanomaterials, the types and characteristics of the interacting biosystems, and the properties of the surrounding microenvironments. Over the years, different experimental approaches coupled with computational modeling have revealed important insights into these interactions, although many outstanding questions remain unanswered. The emergence of machine learning has provided a timely and unique opportunity to revisit nanomaterial-biosystem interactions and to further push the boundary of this field. This minireview highlights the development and use of machine learning to decode nanomaterial-biosystem interactions and provides our perspectives on the current challenges and potential opportunities in this field.
• Kenry, . (2024). Machine-learning-guided quantitative delineation of cell morphological features and responses to nanomaterials. Nanoscale, 16(42), 19656-19668.
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  Delineation of cell morphological features is essential to decipher cell responses to external stimuli like theranostic nanomaterials. Conventional methods rely on labeled approaches, such as fluorescence imaging and flow cytometry, to assess cell responses. Besides potentially perturbing cell structure and morphology, these approaches are relatively complex, time-consuming, expensive, and may not be compatible with downstream analysis involving live cells. Herein, leveraging label-free phase-contrast or brightfield microscopy imaging and machine learning, the delineation of different cell types, phenotypes, and states for monitoring live cell responses is reported. Notably, pixel classification based on a supervised random forest classifier is used to distinguish between cells and backgrounds from the microscopy images, followed by cell segmentation and morphological feature extraction. Quantitative analysis shows that most of the compared cell groups have distinguishable size and shape features. Principal component analysis and unsupervised -means clustering of morphological features reveal the possible existence of heterogenous cell subpopulations and treatment responses among the seemingly homogenous cell groups. This shows the merit of the reported approach in complementing conventional techniques for cell analysis. It is anticipated that the demonstrated method will further aid the implementation of machine learning to streamline the analysis of cell morphology and responses for early disease diagnosis and treatment response monitoring.
• Kenry, . (2024). Microfluidic-assisted formulation of cell membrane-camouflaged anisotropic nanostructures. Nanoscale, 16(16), 7874-7883.
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  Anisotropic gold (Au) nanostructures have been widely explored for various nanomedicine applications. While these nanomaterials have shown great promise for disease theranostics, particularly for cancer diagnosis and treatment, the utilization and clinical translation of anisotropic Au nanostructures have been limited by their high phagocytic uptake and clearance and low cancer targeting specificity. Numerous efforts have thus been made toward mitigating these challenges. Many conventional strategies, however, rely on all-synthetic materials, involve complex chemical processes, or have low product throughput and reproducibility. Herein, by integrating cell membrane coating and microfluidic technologies, a high-throughput bioinspired approach for synthesizing biomimetic anisotropic Au nanostructures with minimized phagocytic uptake and improved cancer cell targeting is reported. Through continuous hydrodynamic flow focusing, mixing, and sonication, Au nanostructures are encapsulated within the macrophage and cancer cell membrane vesicles effectively. The fabricated nanostructures are uniform and highly stable in serum. Importantly, the macrophage membrane vesicle-encapsulated Au nanostructures can be preferentially internalized by breast cancer cells, but not by macrophages. Overall, this study has demonstrated the feasibility of employing an integrated microfluidic-sonication technique to formulate uniform and highly stable biomimetic anisotropic nanostructures for enhanced cancer theranostic applications.
• Sahli, C., & Kenry, F. (2024). Enhancing nanomaterial-based optical spectroscopic detection of cancer through machine learning. ACS Materials Letters, 6(10), 4697-4709. doi:10.1021/acsmaterialslett.4c01267
• Wu, B., Kenry, F., & Hu, F. (2024). Targeted antibacterial photodynamic therapy with aggregation-induced emission photosensitizers. Interdisciplinary Medicine, 2(1), e20230038. doi:10.1002/INMD.20230038
• Wang, P., Liu, J., Zhu, X., Kenry, ., Yan, Z., Yan, J., Jiang, J., Fu, M., Ge, J., Zhu, Q., & Zheng, Y. (2023). Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan. Nature communications, 14(1), 3973.
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  Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has excellent regioselectivity and high tolerance of functional groups which enable late-stage cyclization of peptides. This architecture of cyclic peptides exhibits higher bioactivity than its parent linear peptides. Moreover, the Trp-substituted maleimide displays excellent reactivity toward Michael addition, indicating its potential as a click functional group for applications in chemical biology and medicinal chemistry. As a proof of principle, RGD-GFLG-DOX, which is a peptide-drug-conjugate, is constructed and it displays a strong binding affinity and high antiproliferative activity toward integrin-αvβ overexpressed cancer cell lines. The proposed strategy for rapid preparation of stapled peptides would be a robust tool for creating peptide-drug conjugates.
• Andreiuk, B., Nicolson, F., Clark, L. M., Panikkanvalappil, S. R., Kenry, ., Rashidian, M., Harmsen, S., & Kircher, M. F. (2022). Design and synthesis of gold nanostars-based SERS nanotags for bioimaging applications. Nanotheranostics, 6(1), 10-30.
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  Surface-enhanced Raman spectroscopy (SERS) nanotags hold a unique place among bioimaging contrast agents due to their fingerprint-like spectra, which provide one of the highest degrees of detection specificity. However, in order to achieve a sufficiently high signal intensity, targeting capabilities, and biocompatibility, all components of nanotags must be rationally designed and tailored to a specific application. Design parameters include fine-tuning the properties of the plasmonic core as well as optimizing the choice of Raman reporter molecule, surface coating, and targeting moieties for the intended application. This review introduces readers to the principles of SERS nanotag design and discusses both established and emerging protocols of their synthesis, with a specific focus on the construction of SERS nanotags in the context of bioimaging and theranostics.
• Kenry, ., Nicolson, F., Clark, L., Panikkanvalappil, S. R., Andreiuk, B., & Andreou, C. (2022). Advances in Surface Enhanced Raman Spectroscopy for Imaging in Oncology. Nanotheranostics, 6(1), 31-49.
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  In the last two decades, the application of surface enhanced Raman scattering (SERS) nanoparticles for preclinical cancer imaging has attracted increasing attention. Raman imaging with SERS nanoparticles offers unparalleled sensitivity, providing a platform for molecular targeting, and granting multiplexed and multimodal imaging capabilities. Recent progress has been facilitated not only by the optimization of the SERS contrast agents themselves, but also by the developments in Raman imaging approaches and instrumentation. In this article, we review the principles of Raman scattering and SERS, present advances in Raman instrumentation specific to cancer imaging, and discuss the biological means of ensuring selective uptake of SERS contrast agents for targeted, multiplexed, and multimodal imaging applications. We offer our perspective on areas that must be addressed in order to facilitate the clinical translation of SERS contrast agents for imaging in oncology.
• Kenry, ., Sun, L., Yeo, T., Middha, E., Gao, Y., Lim, C. T., Watanabe, S., & Liu, B. (2022). In Situ Visualization of Dynamic Cellular Effects of Phospholipid Nanoparticles via High-Speed Scanning Ion Conductance Microscopy. Small (Weinheim an der Bergstrasse, Germany), 18(37), e2203285.
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  Phospholipid nanoparticles have been actively employed for numerous biomedical applications. A key factor in ensuring effective and safe applications of these nanomaterials is the regulation of their interactions with target cells, which is significantly dependent on an in-depth understanding of the nanoparticle-cell interactions. To date, most studies investigating these nano-bio interactions have been performed under static conditions and may lack crucial real-time information. It is, however, noteworthy that the nanoparticle-cell interactions are highly dynamic. Consequently, to gain a deeper insight into the cellular effects of phospholipid nanoparticles, real-time observation of cellular dynamics after nanoparticle introduction is necessary. Herein, a proof-of-concept in situ visualization of the dynamic cellular effects of sub-100 nm phospholipid nanoparticles using high-speed scanning ion conductance microscopy (HS-SICM) is reported. It is revealed that upon introduction into the cellular environment, within a short timescale of hundreds of seconds, phospholipid nanoparticles can selectively modulate the edge motility and surface roughness of healthy fibroblast and cancerous epithelial cells. Furthermore, the dynamic deformation profiles of these cells can be selectively altered in the presence of phospholipid nanoparticles. This work is anticipated to further shed light on the real-time nanoparticle-cell interactions for improved formulation of phospholipid nanoparticles for numerous bioapplications.
• Fu, M., Sun, Y., Kenry, ., Zhang, M., Zhou, H., Shen, W., Hu, Y., & Zhu, Q. (2021). A dual-rotator fluorescent probe for analyzing the viscosity of mitochondria and blood. Chemical communications (Cambridge, England), 57(28), 3508-3511.
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  A novel mitochondria-targeting molecular rotator FD was designed to visualize changes in viscosity under hypoxic conditions in vitro and in vivo. Importantly, FD can be used to detect changes in the blood viscosity of liver cancer and liver cirrhosis patients, and also rehabilitation of liver disease.
• Kenry, ., Yeo, T., She, D. T., Nai, M. H., Marcelo Valerio, V. L., Pan, Y., Middha, E., Lim, C. T., & Liu, B. (2021). Differential Collective Cell Migratory Behaviors Modulated by Phospholipid Nanocarriers. ACS nano, 15(11), 17412-17425.
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  Phospholipid nanocarriers have been widely explored for theranostic and nanomedicine applications. These amphiphilic nanocarriers possess outstanding cargo encapsulation efficiency, high water dispersibility, and excellent biocompatibility, which render them promising for drug delivery and bioimaging applications. While the biological applications of phospholipid nanocarriers have been well documented, the fundamental aspects of the phospholipid-cell interactions beyond cytotoxicity have been less investigated. In particular, the effect of phospholipid nanocarriers on collective cell behaviors has not been elucidated. Herein, we evaluate the interactions of phospholipid nanocarriers possessing different functional groups and sizes with normal and cancerous immortalized breast epithelial cell sheets with varying metastatic potential. Specifically, we examine the impact of nanocarrier treatments on the collective migratory dynamics of these cell sheets. We observe that phospholipid nanocarriers induce differential collective cell migratory behaviors, where the migration speed of normal and cancerous breast epithelial cell sheets is retarded and accelerated, respectively. To a certain extent, the nanocarriers are able to alter the migration trajectory of the cancerous breast epithelial cells. Furthermore, phospholipid nanocarriers could modulate the stiffness of the nuclei, cytoplasm, and cell-cell junctions of the breast epithelial cell sheets, remodel their actin filament arrangement, and regulate the expressions of the actin-related proteins. We anticipate that this work will further shed light on nanomaterial-cell interactions and provide guidelines for rational and safer designs and applications of phospholipid nanocarriers for cancer theranostics and nanomedicine.
• Liu, J., Wang, P., Yan, Z., Yan, J., Kenry, ., & Zhu, Q. (2021). Recent Advances in Late-Stage Construction of Stapled Peptides via C-H Activation. Chembiochem : a European journal of chemical biology, 22(18), 2762-2771.
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  Stapled peptides have been widely applied in many fields, including pharmaceutical chemistry, diagnostic reagents, and materials science. However, most traditional stapled peptide preparation methods rely on prefunctionalizations, which limit the diversity of stapled peptides. Recently, the emergence of late-stage transition metal-catalyzed C-H activation in amino acids and peptides has attracted wide interest due to its robustness and applicability for peptide stapling. In this review, we summarize the methods for late-stage construction of stapled peptides via transition metal-catalyzed C-H activation.
• Xu, S., Duan, Y., Manghnani, P., Kenry, ., Chen, C., Kozlov, S. M., & Liu, B. (2021). Stereoisomerization during Molecular Packing. Advanced materials (Deerfield Beach, Fla.), 33(23), e2100986.
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  Isomerization is an essential chemical process that often evokes dramatic change of chemical, physical, or biological properties. For a long time, isomerization has been known as a transformation that is induced by certain external energy such as light, heat, or mechanical force. Herein, a new isomerization phenomenon is described, which does not require external energy but simply occurs during molecular packing. The proposed isomerization is demonstrated by a series of symmetric donor-acceptor-donor (D-A-D) molecules, the donor of which may adopt two different stereoisomeric forms. Based on the evidence of the asymmetric isomers in crystals, the occurrence of isomerization during molecular packing is proved. Moreover, the unique asymmetric geometry in the solid state favors the restriction of intramolecular motion, resulting in highly efficient organic solids with quantum yields approaching unity.
• Chen, H., Li, S., Wu, M., Kenry, ., Huang, Z., Lee, C. S., & Liu, B. (2020). Membrane-Anchoring Photosensitizer with Aggregation-Induced Emission Characteristics for Combating Multidrug-Resistant Bacteria. Angewandte Chemie (International ed. in English), 59(2), 632-636.
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  Traditional photosensitizers (PSs) show reduced singlet oxygen ( O ) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non-targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water-dispersible membrane anchor (TBD-anchor) PS with aggregation-induced emission is designed and synthesized to generate O on the bacterial membrane. TBD-anchor showed efficient antibacterial performance towards both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin-resistant S. aureus (MRSA) when they were exposed to 0.8 μm of TBD-anchor at a low white light dose (25 mW cm ) for 10 minutes. TBD-anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug-resistant bacteria.
• Hu, F., Qi, G., Kenry, ., Mao, D., Zhou, S., Wu, M., Wu, W., & Liu, B. (2020). Visualization and In Situ Ablation of Intracellular Bacterial Pathogens through Metabolic Labeling. Angewandte Chemie (International ed. in English), 59(24), 9288-9292.
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  Protected by the host cells, the hidden intracellular bacteria are typically difficult to kill by common antibiotics and cannot be visualized without complex cellular pretreatments. Herein, we successfully developed a bacteria-metabolizable dual-functional probe TPEPy-d-Ala, which is based on d-alanine and a photosensitizer with aggregation-induced emission for fluorescence turn-on imaging of intracellular bacteria in living host cells and photodynamic ablation in situ. Once metabolically incorporated into bacterial peptidoglycan, the intramolecular motions of TPEPy-d-Ala are inhibited, leading to an enhanced fluorescent signal, which allows the clear visualization of the intracellular bacteria. Moreover, TPEPy-d-Ala can effectively ablate the labeled intracellular bacteria in situ owing to covalent ligation to peptidoglycan, yielding a low intracellular minimum inhibitory concentration (MIC) of 20±0.5 μg mL , much more efficient than that of a commonly used antibiotic, vancomycin.
• Kenry, ., Yeo, T., Manghnani, P. N., Middha, E., Pan, Y., Chen, H., Lim, C. T., & Liu, B. (2020). Mechanistic Understanding of the Biological Responses to Polymeric Nanoparticles. ACS nano, 14(4), 4509-4522.
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  Polymeric nanoparticles play important roles in the delivery of a multitude of therapeutic and imaging contrast agents. Although these nanomaterials have shown tremendous potential in disease diagnosis and therapy, there have been many reports on the failure of these nanoparticles in realizing their intended objectives due to an individual or a combination of factors, which have collectively challenged the merit of nanomedicine for disease theranostics. Herein, we investigate the interactions of polymeric nanoparticles with biological entities from molecular to organism levels. Specifically, the protein corona formation, endothelial uptake, and circulation time of these nanoparticles are systematically probed. We identify the crucial role of nanocarrier lipophilicity, zeta-potential, and size in controlling the interactions between nanoparticles and biological systems and propose a two-step framework in formulating a single nanoparticle system to regulate multiple biological effects. This study provides insight into the rational design and optimization of the performance of polymeric nanoparticles to advance their theranostic and nanomedicine applications.
• Mao, D., Hu, F., Yi, Z., Kenry, ., Xu, S., Yan, S., Luo, Z., Wu, W., Wang, Z., Kong, D., Liu, X., & Liu, B. (2020). AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation. Science advances, 6(26), eabb2712.
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  Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near-infrared (NIR)-driven immunostimulants, based on coupling upconversion nanoparticles with aggregation-induced emission luminogens (AIEgens), to integrate the immunological effects of ROS for enhanced adaptive antitumor immune responses. Intratumorally injected AIEgen-upconversion nanoparticles produce high-dose ROS under high-power NIR irradiation, which induces immunogenic cell death and antigen release. These nanoparticles can also capture the released antigens and deliver them to lymph nodes. Upon subsequent low-power NIR treatment of lymph nodes, low-dose ROS are generated to further trigger efficient T cell immune responses through activation of dendritic cells, preventing both local tumor recurrence and distant tumor growth. The utility of dual-mode pumping power on AIEgen-coupled upconversion nanoparticles offers a powerful and controllable platform to activate adaptive immune systems for tumor immunotherapy.
• Mao, D., Zhang, C., Kenry, ., Liu, J., Wang, X., Li, B., Yan, H., Hu, F., Kong, D., Wang, Z., & Liu, B. (2020). Bio-orthogonal click reaction-enabled highly specific in situ cellularization of tissue engineering scaffolds. Biomaterials, 230, 119615.
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  Tissue engineering generally utilizes natural or synthetic scaffolds to repair or replace damaged tissues. However, due to the lack of guidance of biological signals, most of the implanted scaffolds have always suffered from poor in vivo cellularization. Herein, we demonstrate a bio-orthogonal reaction-based strategy to realize in situ specific and fast cellularization of tissue engineering scaffold. DBCO-modified PCL-PEG (PCL-PEG-DBCO) polymer was synthesized and then fabricated into PCL-PEG-DBCO film through electrospinning. Meanwhile, azide-labeled macrophages (N (+) macrophages) were obtained through metabolic glycoengineering. Through a series of in vitro dynamic and in vivo characterization, DBCO-modified films were noted to dramatically increase the selective capture efficiency and survival rate of N (+) cells. Additionally, there is negligible influence of covalent conjugation on cell viability and proliferation, indicating the feasibility of the bio-orthogonal click reaction-based tissue engineering strategy. Overall, this work shows the advantages of an in situ bio-orthogonal click reaction in realizing highly specific, efficient, and long-lasting scaffold cellularization. We anticipate that this general strategy would be widely applicable and useful in tissue engineering and regenerative medicine in the near future.
• Yoshino, D., Funamoto, K., Sato, K., Kenry, ., Sato, M., & Lim, C. T. (2020). Hydrostatic pressure promotes endothelial tube formation through aquaporin 1 and Ras-ERK signaling. Communications biology, 3(1), 152.
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  Vascular tubulogenesis is tightly linked with physiological and pathological events in the living body. Endothelial cells (ECs), which are constantly exposed to hemodynamic forces, play a key role in tubulogenesis. Hydrostatic pressure in particular has been shown to elicit biophysical and biochemical responses leading to EC-mediated tubulogenesis. However, the relationship between tubulogenesis and hydrostatic pressure remains to be elucidated. Here, we propose a specific mechanism through which hydrostatic pressure promotes tubulogenesis. We show that pressure exposure transiently activates the Ras/extracellular signal-regulated kinase (ERK) pathway in ECs, inducing endothelial tubulogenic responses. Water efflux through aquaporin 1 and activation of protein kinase C via specific G protein-coupled receptors are essential to the pressure-induced transient activation of the Ras/ERK pathway. Our approach could provide a basis for elucidating the mechanopathology of tubulogenesis-related diseases and the development of mechanotherapies for improving human health.
• Dou, Y., Kenry, ., Liu, J., Zhang, F., Cai, C., & Zhu, Q. (2019). 2-Styrylquinoline-based two-photon AIEgens for dual monitoring of pH and viscosity in living cells. Journal of materials chemistry. B, 7(48), 7771-7775.
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  A new class of aggregation-induced emission (AIE) fluorophores HAPHs with excellent two-photon properties is developed from styrylquinoline. Among them, the probe HAPH-1 exhibits good sensitivity towards pH and viscosity and has been successfully used for simultaneous pH and viscosity detection in living cells through two-photon microscopy.
• Gao, Y., Zheng, Q. C., Xu, S., Yuan, Y., Cheng, X., Jiang, S., Kenry, ., Yu, Q., Song, Z., Liu, B., & Li, M. (2019). Theranostic Nanodots with Aggregation-Induced Emission Characteristic for Targeted and Image-Guided Photodynamic Therapy of Hepatocellular Carcinoma. Theranostics, 9(5), 1264-1279.
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  Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin αβ-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS. The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both and . The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining. The obtained nanodots show bright red fluorescence and highly effective O generation in aggregate state. Both and experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis the mitochondria-mediated pathway is achieved under low PDT intensity. Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.
• Kenry, ., Chen, C., & Liu, B. (2019). Enhancing the performance of pure organic room-temperature phosphorescent luminophores. Nature communications, 10(1), 2111.
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  Once considered the exclusive property of metal complexes, the phenomenon of room-temperature phosphorescence (RTP) has been increasingly realized in pure organic luminophores recently. Using precise molecular design and synthetic approaches to modulate their weak spin-orbit coupling, highly active triplet excitons, and ultrafast deactivation, organic luminophores can be endowed with long-lived and bright RTP characteristics. This has sparked intense explorations into organic luminophores with enhanced RTP features for different applications. This Review discusses the fundamental mechanism of RTP in pure organic luminophores, followed by design principles, enhancement strategies, and formulation methods to achieve highly phosphorescent and long-lived organic RTP luminophores even in aqueous media. The current challenges and future directions of this field are also discussed in the summary and outlook.
• Kenry, ., Chong, K. C., & Liu, B. (2019). Reactivity-Based Organic Theranostic Bioprobes. Accounts of chemical research, 52(11), 3051-3063.
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  Reactivity-based organic bioprobes have been increasingly designed and developed in the last couple of years to address important questions in numerous fields, particularly in biology and medicine. Contrary to the conventional lock-and-key bioprobes, which rely on molecular recognition to probe biological systems and impart sensing specificity, reactivity-based bioprobes capitalize on molecular reactivity for selective target detection. In fact, reactivity-based sensing exploits the intrinsic differences in chemical reactivity to differentiate various chemical species possessing similar size and shape in biological systems. This unique sensing mechanism has been effective for the detection of a wide range of chemical analytes in living cells, tissues, and animals, although bioprobes with additional functionalities are increasingly required in the quest to unravel and understand the complex biological systems. This is why the integration of diagnostic and therapeutic functions in one theranostic platform has become a continuous pursuit in the development of bioprobes in recent years. To this end, numerous design and synthetic approaches have been explored, notably that combining different organic materials with distinct functionalities into one integrated system, also known as "all-in-one" strategy. Nevertheless, the "all-in-one" strategy is prone to design complexity and unsatisfactory reproducibility. To minimize these undesirable hurdles, the deliberate design and engineering of simple organic molecules with multiple functionalities have been actively pursued, leading to the emergence of a unique approach known as "one-for-all" strategy. A prominent example of this approach leverages on fluorogens with aggregation-induced emission (AIE) characteristic. Through smart molecular engineering, we and other groups have recently shown that conventional organic AIE fluorogens can be specifically tailored to offer both imaging and therapeutic functionalities, such as photosensitizing ability to facilitate photodynamic therapy. The creation of this new class of versatile organic theranostic bioprobes with simultaneous imaging and therapeutic capabilities has further enabled image-guided chemotherapy and image-guided photodynamic therapy. Essentially, from this endeavor, replacing the fluorophores of conventional reactivity-based bioprobes with multifunctional molecules will yield reactivity-based organic theranostic bioprobes with enhanced capabilities and improved performance. In this Account, we summarize the latest advancement of reactivity-based theranostic bioprobes. To start with, we discuss the fundamental differences between conventional lock-and-key and reactivity-based sensing mechanisms, followed by general design routes of reactivity-based organic theranostic bioprobes. We then describe our efforts in recent years in formulating reactivity-based organic biosensing/imaging probes and multifunctional theranostic probes as well as in utilizing these bioprobes in detecting various chemical species in living systems, such as free radicals and toxins, and in diagnosing and treating cancer and bacterial infections. Finally, we highlight current challenges and opportunities in the conclusions and outlook section. With this Account, we seek to further stimulate research activities and closer collaborations among the research fields of chemistry, materials, and biology to push the boundary of this emerging field and promote reactivity-based theranostics for practical applications and clinical translations.
• Qi, G., Hu, F., Kenry, ., Shi, L., Wu, M., & Liu, B. (2019). An AIEgen-Peptide Conjugate as a Phototheranostic Agent for Phagosome-Entrapped Bacteria. Angewandte Chemie (International ed. in English), 58(45), 16229-16235.
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  The detection and elimination of intracellular bacteria remain a major challenge. In this work, we report an aggregation-induced emission (AIE) bioprobe that can detect bacterial infection and kill bacteria surviving inside macrophages through a dynamic process, notably specific molecular tailoring of the probe by caspase-1 activation in infected macrophages and accumulation of the residue on phagosomes containing bacteria, leading to light-up fluorescent signals. Moreover, the AIEgen can serve as a photosensitizer for generation of reactive oxygen species (ROS); and the average ROS indicator fluorescent signal intensity per unit area in the bacterial phagosomes is approximately 2.7-fold higher than that in the cytoplasm. This, in turn, induces bacteria killing with high efficiency and minimal cytotoxicity towards macrophages. We envision that this specific light-up bioprobe may provide a new approach for selective and sensitive detection and eradication of intracellular bacterial infections.
• Yeo, J. C., Kenry, ., Zhao, Z., Zhang, P., Wang, Z., & Lim, C. T. (2018). Label-free extraction of extracellular vesicles using centrifugal microfluidics. Biomicrofluidics, 12(2), 024103.
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  Extracellular vesicles (EVs) play an important role as active messengers in intercellular communication and distant microenvironment modeling. Increasingly, these EVs are recognized as important biomarkers for clinical diagnostics. However, current isolation methods of EVs are time-consuming and ineffective due to the high diffusive characteristics of nanoparticles coupled with fluid flow instability. Here, we develop a microfluidic CEntrifugal Nanoparticles Separation and Extraction (µCENSE) platform for the rapid and label-free isolation of microvesicles. By utilizing centrifugal microhydrodynamics, we subject the nanosuspensions between 100 nm and 1000 nm to a unique fluid flow resulting in a zonal separation into different outlets for easy post-processing. Our centrifugal platform utilizes a gentle and efficient size-based separation without the requirements of syringe pump and other accessories. Based on our results, we report a high separation efficiency of 90% and an extraction purity of 85% within a single platform. Importantly, we demonstrate high EV extraction using a table top centrifuge within a short duration of eight minutes. The simple processes and the small volume requirement further enhance the utility of the platform. With this platform, it serves as a potential for liquid biopsy extraction and point-of-care diagnostics.