People
Research Fellow
Wilson Soh
Title
Research Fellow
Degree
PhD
Research Interests
Drug delivery, Bioimaging, Nanomedicine, Smart nanomaterials, Assay development
Research Group
Office Location
S9-08-01-41
I-FIM Publications:
2025 |
Chan, Samuel Jun Wei; Xiao, Zhaolin; Soh, Wilson Wee Mia; Zhu, Ji-Yu; Lopez-Garcia, Fernando; Deng, Hui; Bazan, Guillermo Carlos Membrane Intercalation of a Conjugated Oligoelectrolyte Photosensitizer Enables Efficient Anticancer Photodynamic Therapy ADVANCED HEALTHCARE MATERIALS, 14 (18), 2025, DOI: 10.1002/adhm.202501300. @article{WOS:001494493300001, title = {Membrane Intercalation of a Conjugated Oligoelectrolyte Photosensitizer Enables Efficient Anticancer Photodynamic Therapy}, author = {Samuel Jun Wei Chan and Zhaolin Xiao and Wilson Wee Mia Soh and Ji-Yu Zhu and Fernando Lopez-Garcia and Hui Deng and Guillermo Carlos Bazan}, doi = {10.1002/adhm.202501300}, times_cited = {3}, issn = {2192-2640}, year = {2025}, date = {2025-07-01}, journal = {ADVANCED HEALTHCARE MATERIALS}, volume = {14}, number = {18}, publisher = {WILEY-V C H VERLAG GMBH}, address = {POSTFACH 101161, 69451 WEINHEIM, GERMANY}, abstract = {Photodynamic therapy (PDT) complements traditional chemotherapeutic methods by leveraging an external optical stimulus to target and eradicate tumor cells. Photosensitizers with favorable photophysical properties are, however, often hampered by poor biodistribution and inadequate cellular uptake, highlighting the need for novel molecular design strategies. Conjugated oligoelectrolytes (COEs) are a class of optical reporters that readily incorporate within cells due to their lipid bilayer mimicking molecular topology. Herein, a COE-derived photosensitizer, COE-PP, which features a central porphyrin core flanked by ionic pendant groups is disclosed. COE-PP has a solubility in aqueous media of >20 mm, yet the membrane-mimicking molecular topology enables high cellular uptake and prolonged retention of the COE in vitro and in vivo of up to 21 days. COE-PP is an effective phototheranostic agent for simultaneous tumor imaging and eradication, with the generation of reactive oxygen species (ROS) upon illumination. The membrane localization of COE-PP promotes cell death during PDT by ROS and through downstream pathways involving lysosomal membrane permeabilization. These synergistic effects enable effective treatment of COE-containing tumors. From a broad design perspective, the molecular architecture of COE-PP demonstrates the potential of utilizing lipid bilayer-mimicking molecular topologies to design phototheranostic molecules that offer spatiotemporal control for therapeutic interventions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Photodynamic therapy (PDT) complements traditional chemotherapeutic methods by leveraging an external optical stimulus to target and eradicate tumor cells. Photosensitizers with favorable photophysical properties are, however, often hampered by poor biodistribution and inadequate cellular uptake, highlighting the need for novel molecular design strategies. Conjugated oligoelectrolytes (COEs) are a class of optical reporters that readily incorporate within cells due to their lipid bilayer mimicking molecular topology. Herein, a COE-derived photosensitizer, COE-PP, which features a central porphyrin core flanked by ionic pendant groups is disclosed. COE-PP has a solubility in aqueous media of >20 mm, yet the membrane-mimicking molecular topology enables high cellular uptake and prolonged retention of the COE in vitro and in vivo of up to 21 days. COE-PP is an effective phototheranostic agent for simultaneous tumor imaging and eradication, with the generation of reactive oxygen species (ROS) upon illumination. The membrane localization of COE-PP promotes cell death during PDT by ROS and through downstream pathways involving lysosomal membrane permeabilization. These synergistic effects enable effective treatment of COE-containing tumors. From a broad design perspective, the molecular architecture of COE-PP demonstrates the potential of utilizing lipid bilayer-mimicking molecular topologies to design phototheranostic molecules that offer spatiotemporal control for therapeutic interventions.
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Zhu, Ji-Yu; Chan, Samuel J W; Cui, Hongyue; Mikhalovsky, Alexander A; Garcia, Fernando L; Goh, Brandon Yeow Wee; Soh, Wilson Wee Mia; Moreland, Alex S; Limwongyut, Jakkarin; Shyamasundar, Sukanya; Wu, Ya Jun; Liang, Fengyi; Li, Rong; Bazan, Guillermo C Mechanosensitive Conjugated Oligoelectrolytes for Visualizing Temporal Changes in Live Cells ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2025, DOI: 10.1002/anie.202506396. @article{WOS:001484938900001, title = {Mechanosensitive Conjugated Oligoelectrolytes for Visualizing Temporal Changes in Live Cells}, author = {Ji-Yu Zhu and Samuel J W Chan and Hongyue Cui and Alexander A Mikhalovsky and Fernando L Garcia and Brandon Yeow Wee Goh and Wilson Wee Mia Soh and Alex S Moreland and Jakkarin Limwongyut and Sukanya Shyamasundar and Ya Jun Wu and Fengyi Liang and Rong Li and Guillermo C Bazan}, doi = {10.1002/anie.202506396}, times_cited = {4}, year = {2025}, date = {2025-05-01}, journal = {ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, publisher = {WILEY-V C H VERLAG GMBH}, address = {POSTFACH 101161, 69451 WEINHEIM, GERMANY}, abstract = {Membrane-intercalating conjugated oligoelectrolytes (COEs) are lipid-bilayer-spanning molecules that serve as fluorescent dyes for bioimaging. However, COE emission has thus far only been capable of visualizing dye location and their preferential accumulation in different membrane-bound intracellular compartments. Herein, we report the first example of environmentally sensitive COEs for visualizing temporal changes in live cells, providing information on the physical properties of intracellular lipid bilayer membranes. The new COE-BY series is designed around a BODIPY central unit with a membrane-spanning topology and six cationic pendant groups ensuring solubility in aqueous media. These reporters feature high two-photon absorption cross section, NIR-II excitation capabilities under multiphoton excitation, and high dye brightness; all highly desirable photophysical features for bioimaging. The emission lifetime of the probes was sensitive to changes to both the lipid composition of model vesicle systems and membrane tension within cells, induced by either mechanical or osmotic stress. Using two-photon fluorescence lifetime imaging microscopy, it is possible to use the most efficient emitter, namely, COE-BYPhOC4, to image changes in the mechanical properties of intracellular membranes. We show that these COEs remain stably vesicle-bound within the endolysosomal pathway over extended periods, allowing for long-term monitoring of the associated biophysical changes of these vesicles over time.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Membrane-intercalating conjugated oligoelectrolytes (COEs) are lipid-bilayer-spanning molecules that serve as fluorescent dyes for bioimaging. However, COE emission has thus far only been capable of visualizing dye location and their preferential accumulation in different membrane-bound intracellular compartments. Herein, we report the first example of environmentally sensitive COEs for visualizing temporal changes in live cells, providing information on the physical properties of intracellular lipid bilayer membranes. The new COE-BY series is designed around a BODIPY central unit with a membrane-spanning topology and six cationic pendant groups ensuring solubility in aqueous media. These reporters feature high two-photon absorption cross section, NIR-II excitation capabilities under multiphoton excitation, and high dye brightness; all highly desirable photophysical features for bioimaging. The emission lifetime of the probes was sensitive to changes to both the lipid composition of model vesicle systems and membrane tension within cells, induced by either mechanical or osmotic stress. Using two-photon fluorescence lifetime imaging microscopy, it is possible to use the most efficient emitter, namely, COE-BYPhOC4, to image changes in the mechanical properties of intracellular membranes. We show that these COEs remain stably vesicle-bound within the endolysosomal pathway over extended periods, allowing for long-term monitoring of the associated biophysical changes of these vesicles over time.
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Soh, Wilson Wee Mia; Finol, Esteban; Chan, Samuel J W; Zhu, Ji-Yu; Liau, Sebastian Sean Jing Kang; Bier, Ava; Ooi, Eng Eong; Bazan, Guillermo C Tailoring Lipid Nanoparticle with Ex Situ Incorporated Conjugated Oligoelectrolyte for Enhanced mRNA Delivery Efficiency ADVANCED HEALTHCARE MATERIALS, 14 (14), 2025, DOI: 10.1002/adhm.202405048. @article{WOS:001450864700001, title = {Tailoring Lipid Nanoparticle with Ex Situ Incorporated Conjugated Oligoelectrolyte for Enhanced mRNA Delivery Efficiency}, author = {Wilson Wee Mia Soh and Esteban Finol and Samuel J W Chan and Ji-Yu Zhu and Sebastian Sean Jing Kang Liau and Ava Bier and Eng Eong Ooi and Guillermo C Bazan}, doi = {10.1002/adhm.202405048}, times_cited = {1}, issn = {2192-2640}, year = {2025}, date = {2025-05-01}, journal = {ADVANCED HEALTHCARE MATERIALS}, volume = {14}, number = {14}, publisher = {WILEY-V C H VERLAG GMBH}, address = {POSTFACH 101161, 69451 WEINHEIM, GERMANY}, abstract = {Developing new lipid nanoparticle (LNP) formulations typically involves reconstruction from separate elements followed by rigorous purification steps, contributing to drawn-out drug discovery processes. Membrane-intercalating conjugated oligoelectrolytes (COEs) are water-soluble molecules featuring a conjugated backbone and peripheral ionic groups, specifically designed to spontaneously integrate into lipid bilayers. Herein, an ex situ strategy to ``dope'' the representative COE-S6 into pre-formed messenger RNA-LNPs (mRNA-LNPs) is presented, exploiting its spontaneous membrane intercalation property through a straightforward add-and-mix procedure. Incorporating 0.2% COE-S6 into mRNA-LNPs relative to lipid content reduced particle size from 84.5 +/- 1 to 67.9 +/- 0.8 nm, elevated cellular uptake, and improved endosomal escape. These traits culminate in an increase in in cellula transfection from 24.2 +/- 1.6% to 98.7 +/- 0.6%. When injected intravenously into healthy BALB/c mice, the optimized COE-S6-doped mRNA-LNPs boost in vivo luciferase expression by 1.75-fold. Additionally, COE-S6-doped mRNA-LNPs exhibit fluorogenic properties, enabling intracellular mechanistic studies via confocal microscopy. This simple method enhances the properties of mRNA-LNPs with minimal COE quantities, offering a novel strategy to improve existing LNP formulations and provide optical reporting capabilities, essential for expediting drug discovery and delivery.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Developing new lipid nanoparticle (LNP) formulations typically involves reconstruction from separate elements followed by rigorous purification steps, contributing to drawn-out drug discovery processes. Membrane-intercalating conjugated oligoelectrolytes (COEs) are water-soluble molecules featuring a conjugated backbone and peripheral ionic groups, specifically designed to spontaneously integrate into lipid bilayers. Herein, an ex situ strategy to ``dope'' the representative COE-S6 into pre-formed messenger RNA-LNPs (mRNA-LNPs) is presented, exploiting its spontaneous membrane intercalation property through a straightforward add-and-mix procedure. Incorporating 0.2% COE-S6 into mRNA-LNPs relative to lipid content reduced particle size from 84.5 +/- 1 to 67.9 +/- 0.8 nm, elevated cellular uptake, and improved endosomal escape. These traits culminate in an increase in in cellula transfection from 24.2 +/- 1.6% to 98.7 +/- 0.6%. When injected intravenously into healthy BALB/c mice, the optimized COE-S6-doped mRNA-LNPs boost in vivo luciferase expression by 1.75-fold. Additionally, COE-S6-doped mRNA-LNPs exhibit fluorogenic properties, enabling intracellular mechanistic studies via confocal microscopy. This simple method enhances the properties of mRNA-LNPs with minimal COE quantities, offering a novel strategy to improve existing LNP formulations and provide optical reporting capabilities, essential for expediting drug discovery and delivery.
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2023 |
Chan, Samuel J W; Zhu, Ji-Yu; Soh, Wilson Wee Mia; Bazan, Guillermo C Real-Time Monitoring of Mitochondrial Damage Using Conjugated Oligoelectrolytes 19 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 146 (1), pp. 660-667, 2023, DOI: 10.1021/jacs.3c10531. @article{WOS:001140785600001, title = {Real-Time Monitoring of Mitochondrial Damage Using Conjugated Oligoelectrolytes}, author = {Samuel J W Chan and Ji-Yu Zhu and Wilson Wee Mia Soh and Guillermo C Bazan}, doi = {10.1021/jacs.3c10531}, times_cited = {19}, issn = {0002-7863}, year = {2023}, date = {2023-12-01}, journal = {JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, volume = {146}, number = {1}, pages = {660-667}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {Conjugated oligoelectrolytes (COEs) comprise a class of fluorescent reporters with tunable optical properties and lipid bilayer affinity. These molecules have proven effective in a range of bioimaging applications; however, their use in characterizing specific subcellular structures remains restricted. Such capabilities would broaden COE applications to understand cellular dysfunction, cell communication, and the targets of different pharmaceutical agents. Here, we disclose a novel COE derivative, COE-CN, which enables the visualization of mitochondria, including morphological changes and lysosomal fusion upon treatment with depolarizing agents. COE-CN is characterized by the presence of imidazolium solubilizing groups and an optically active cyanovinyl-linked distyrylbenzene core with intramolecular charge-transfer characteristics. Our current understanding is that the relatively shorter molecular length of COE-CN leads to weaker binding within lipid bilayer membranes, which allows sampling of internal cellular structures and ultimately to different localization relative to elongated COEs. As a means of practical demonstration, COE-CN can be used to diagnose cells with damaged mitochondria via flow cytometry. Coupled with an elongated COE that does not translocate upon depolarization, changes in ratiometric fluorescence intensity can be used to monitor mitochondrial membrane potential disruption, demonstrating the potential for use in diagnostic assays.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Conjugated oligoelectrolytes (COEs) comprise a class of fluorescent reporters with tunable optical properties and lipid bilayer affinity. These molecules have proven effective in a range of bioimaging applications; however, their use in characterizing specific subcellular structures remains restricted. Such capabilities would broaden COE applications to understand cellular dysfunction, cell communication, and the targets of different pharmaceutical agents. Here, we disclose a novel COE derivative, COE-CN, which enables the visualization of mitochondria, including morphological changes and lysosomal fusion upon treatment with depolarizing agents. COE-CN is characterized by the presence of imidazolium solubilizing groups and an optically active cyanovinyl-linked distyrylbenzene core with intramolecular charge-transfer characteristics. Our current understanding is that the relatively shorter molecular length of COE-CN leads to weaker binding within lipid bilayer membranes, which allows sampling of internal cellular structures and ultimately to different localization relative to elongated COEs. As a means of practical demonstration, COE-CN can be used to diagnose cells with damaged mitochondria via flow cytometry. Coupled with an elongated COE that does not translocate upon depolarization, changes in ratiometric fluorescence intensity can be used to monitor mitochondrial membrane potential disruption, demonstrating the potential for use in diagnostic assays.
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