Daniel Chin Shiuan Lio

Nanyang Technological University

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Chenjie Xu

City University of Hong Kong

Christian Wiraja

Nanyang Technological University

Mengjia Zheng

Zhangzhou Municipal Hospital of Fujian Province

David Yeo

St George Hospital

Hao Chang

Chinese Academy of Sciences

Xiaomeng Wang

Singapore Eye Research Institute

Amy S. Paller

Northwestern University

Chenghao Liu

Institute of Biomedical Sciences, Academia Sinica

Chad A. Mirkin

Northwestern University

Mingyue Cui

Zhengzhou University

Cooperative Institutions

Nanyang Technological University

Agency for Science, Technology and Research

Northwestern University

National University of Singapore

Chinese Academy of Sciences

Duke-NUS Medical School

University of Chinese Academy of Sciences

Institute of Molecular and Cell Biology

City University of Hong Kong

Shanghai Institute of Applied Physics

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Control of Alginate Core Size in Alginate-Poly (Lactic-Co-Glycolic) Acid Microparticles

Nanoscale Research Letters (2016)

Daniel Chin Shiuan Lio David Yeo Chenjie Xu

Core-shell alginate-poly (lactic-co-glycolic) acid (PLGA) microparticles are potential candidates to improve hydrophilic drug loading while facilitating controlled release. This report studies the influence of the alginate core size on the drug release profile of alginate-PLGA microparticles and its size. Microparticles are synthesized through double-emulsion fabrication via a concurrent ionotropic gelation and solvent extraction. The size of alginate core ranges from approximately 10, 50, to 100 μm when the emulsification method at the first step is homogenization, vortexing, or magnetic stirring, respectively. The second step emulsification for all three conditions is performed with magnetic stirring. Interestingly, although the alginate core has different sizes, alginate-PLGA microparticle diameter does not change. However, drug release profiles are dramatically different for microparticles comprising different-sized alginate cores. Specifically, taking calcein as a model drug, microparticles containing the smallest alginate core (10 μm) show the slowest release over a period of 26 days with burst release less than 1 %.

PLGA

Glycolic acid

Microparticle

10.1186/s11671-015-1222-7

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Citations (25)

Cryomicroneedles for transdermal cell delivery

Nature Biomedical Engineering (2021)

Hao Chang Sharon W. T. Chew Mengjia Zheng Daniel Chin Shiuan Lio Christian Wiraja

10.1038/s41551-021-00720-1

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Citations (163)

Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts

Small (2018)

Mengjia Zheng Christian Wiraja David Yeo Hao Chang Daniel Chin Shiuan Lio

Abstract Early diagnosis and timely intervention are key for the successful treatment of skin diseases like abnormal scars. This study introduces a nucleic‐acid‐based probe (i.e., molecular sprinkler) for the diagnosis and spontaneous regulation of the abnormal expression of fibrosis‐related mRNA in scar‐derived skin fibroblasts. Using mRNA encoding connective tissue growth factor (CTGF) as the model gene, a probe with three oligonucleotides is constructed, including a recognition sequence complementary to the CTGF mRNA, a siRNA against transforming growth factor receptor I (TGFβRI) as the CTGF mRNA suppressor, and a connecting sequence. The probe can detect CTGF mRNA with a limit of 10 × 10 −9 m and distinguishes scar fibroblasts from normal ones in both 2D and 3D environments. Two days after transfection, the siRNA released from the probe reduces the expression of TGFβRI and, consequently, decreases the cellular expression of CTGF mRNA (up to 70%). This dual‐role probe presents opportunities to monitor the TGF‐ β signaling pathway, screen for drugs that target the CTGF pathway, and determine the role of inhibition of the CTGF pathway in therapeutic efficacy.

10.1002/smll.201802546

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Citations (15)

The fetal mouse metatarsal bone explant as a model of angiogenesis

Nature Protocols (2015)

Weihua Song Chee Wai Fhu Koon Hwee Ang Chenghao Liu Nurul Azizah Binte Johari

Ex vivo

Sprouting angiogenesis

Vasculogenesis

10.1038/nprot.2015.097

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Citations (34)

Framework nucleic acids as programmable carrier for transdermal drug delivery

Nature Communications (2019)

Christian Wiraja Ying Zhu Daniel Chin Shiuan Lio David Yeo Mo Xie

DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility. However, rapid serum disintegration leads to low bioavailability at targeted sites following systemic administration, hindering their biomedical applications. Here we demonstrate transdermal delivery of framework nucleic acids (FNAs) through topical applications. By designing FNAs with distinct shapes and sizes, we interrogate their penetration on mice and human skin explant. Skin histology reveals size-dependent penetration, with FNAs ≤75 nm effectively reaching dermis layer. 17 nm-tetrahedral FNAs show greatest penetration to 350 µm from skin periphery. Importantly, structural integrity is maintained during the skin penetration. Employing a mouse melanoma model, topical application of doxorubicin-loaded FNAs accommodates ≥2-fold improvement in drug accumulation and tumor inhibition relative to topically-applied free doxorubicin, or doxorubicin loaded in liposomes and polymeric nanoparticles. Programmable penetration with minimal systemic biodistribution underlines FNA potential as localized transdermal drug delivery carriers.

Penetration (warfare)

Biodistribution

Biocompatibility

10.1038/s41467-019-09029-9

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Citations (222)

Osmosis‐Powered Hydrogel Microneedles for Microliters of Skin Interstitial Fluid Extraction within Minutes

Advanced Healthcare Materials (2020)

Mengjia Zheng Zifeng Wang Hao Chang Lulu Wang Sharon W. T. Chew

Abstract Hydrogel microneedle patch enables the extraction of skin interstitial fluid (ISF) through in situ swelling in a minimally invasive manner without assistance of mechano‐chemical peripherals. However, existing hydrogel microneedles require tens of minutes with multistep process to collect sufficient volume (1 mL) for effective analysis. This study introduces an osmolyte‐powered hydrogel microneedle patch that can extract ISF three times faster than the existing platforms and provide in situ analysis of extracted biomarkers. The microneedle patch is composed of osmolytes (i.e., maltose) and hydrogel (i.e., methacrylated hyaluronic acid). During the extraction process, the osmolytes dissolve in the matrix and provide the osmotic pressure that increases the diffusion of ISF from skin to the hydrogel matrix. A patch with 100 microneedles can extract 7.90 µL of ISF from pig skin ex vivo and 3.82 µL of ISF from mouse skin in vivo within 3 min, whereas the control (i.e., hydrogel microneedle without osmolytes) requires >10 min to achieve similar results. The extracted ISF allows the quantification of biomarkers such as glucose and/or drugs such as insulin in vivo. Through the integration with the electronic glucose sensors, the whole system permits the direct and rapid analysis of the extracted glucose.

Interstitial fluid

Osmolyte

10.1002/adhm.201901683

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Citations (149)

Passive and active strategies for transdermal drug delivery with nanotechnology and temporal pressure

Daniel Chin Shiuan Lio

Pressure sensitive

10.32657/10356/136603

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Citations (0)

670 Topical treatment for abnormal scars using spherical nucleic acids

Journal of Investigative Dermatology (2019)

Adam Ponedal Shengshuang Zhu Anthony J. Sprangers X. Wang David Yeo

Keloid

Hypertrophic scars

10.1016/j.jid.2019.03.746

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Targeted Delivery of Anesthetic Agents to Bone Tissues using Conductive Microneedles Enhanced Iontophoresis for Painless Dental Anesthesia

Advanced Functional Materials (2021)

Razina Z. Seeni Mengjia Zheng Daniel Chin Shiuan Lio Christian Wiraja Mohammad Firdaus Bin Mohd Yusoff

Abstract Pain management during dental procedures is a cornerstone for successful daily practice. In current practice, the traditional needle and syringe injection is used to administer local anesthesia. However, the appearance of long needles and the pain associated with it often leads to dental anxiety deterring timely interventions. Microneedles (MNs) have emerged as a minimally invasive alternative to hypodermic needles and shown to be effective in transdermal drug delivery applications. In this article, the potential use of MNs for local anesthesia delivery in dentistry is explored. The development of a novel conductive MN array that can be used in combination with iontophoresis technique to achieve drug penetration through the oral mucosa and the underlying bone tissue is presented. The conductive MN array plays a dual‐role, creating micro‐conduits and lowering the resistance of the oral mucosa. The reduced tissue resistance further enhances the application of a low‐voltage current that is able to direct and accelerate the drug molecules to target the sensory nerves supplying teeth. The successful delivery of lidocaine using this new strategy in a clinically relevant rabbit incisor model is shown to be as effective as the current gold standard.

Iontophoresis

Hypodermic needle

10.1002/adfm.202105686

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Citations (41)

Molecular Beacon Gold Nanosensors for Leucine-Rich Alpha-2-Glycoprotein-1 Detection in Pathological Angiogenesis

ACS Sensors (2018)

Daniel Chin Shiuan Lio Chenghao Liu Christian Wiraja Beiying Qiu Chee Wai Fhu

Leucine-rich alpha-2-glycoprotein-1 (Lrg1) is an emerging biomarker for angiogenesis. Its expression in ocular tissues is up-regulated in both human patients with proliferative diabetic retinopathy and rodent models of pathological angiogenesis. However, there is no existing sensor that allows visualization and monitoring of Lrg1 expression noninvasively and in real time. Herein, we report a nucleic acid-gold nanorod-based nanosensor for the noninvasive monitoring of cellular Lrg1 expression in angiogenesis. Specifically, this platform is constructed by covalently conjugating molecular beacons onto gold nanorods, which prequench the fluorophores on the molecular beacons. Upon intracellular entry and endosomal escape, the complexes interact with cellular Lrg1 mRNA through hybridization of the loop area of the molecular beacons. This complexation distances the fluorophores from nanorod and restores the prequenched fluorescence. The reliability of this platform is confirmed by examining the increased Lrg1 expression in migrating keratinocytes and the Lrg1 gene changes in different postnatal stages of mouse retinal vasculature growth in the mouse retina model.

Molecular beacon

Nanosensor

10.1021/acssensors.8b00321

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Citations (17)