Browsing by Author "Liu, Yibo"

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Mucin-targeting-aptamer functionalized liposomes for delivery of cyclosporin A for dry eye diseases
(Royal Society of Chemistry, 2023-05-03) Wong, Ka-Ying; Liu, Yibo; Zhou, Liping; Wong, Man-Sau; Liu, Juewen
Traditional eye drops are convenient to use; however, their effectiveness is limited by their poor retention time and bioavailability in the eyes due to ocular barriers. Therefore, strategies to enhance ocular drug delivery are required. Herein, we constructed a mucin-1 aptamer-functionalized liposome and loaded it with cyclosporin A, a common ocular drug in eye drops used to treat dry eye diseases (DED). Drug encapsulation slightly reduced the liposome size without changing the surface potential of liposomes. Approximately 90% of the cholesterol-modified aptamers were inserted to the liposomes. We evaluated the cytotoxicity, anti-inflammatory effects, cell permeability regulation, and retention time of liposomes in human corneal epithelial cells under dry eye conditions. These results suggest that the aptamer-functionalized liposomes are more efficient as nanocarriers than non-functionalized liposomes and drug-free liposomes. They restore inflammation levels by 1-fold and remain in the cells for up to 24 h. An in vivo study was also performed in a rat DED model, which demonstrated the efficacy of aptamer-functionalized liposomes in restoring tear production and corneal integrity. The present study demonstrated the capability of aptamer-functionalized liposomes in the delivery of ocular drugs for the management of ocular diseases.
Salt-induced Adsorption and Rupture of Liposomes on Microplastics
(2023-11-07) Fukunaga, Yu; Zandieh, Mohamad; Liu, Yibo; Liu, Juewen
Microplastics have attracted considerable attention because of concerns regarding their environmental risks to living systems. The interaction between the lipid bilayer and microplastics is important for examining the potential harm to biological membranes in the presence of microplastics. In addition, membrane coatings may change the surface and colloidal properties of microplastics. Herein, phosphatidylcholine (PC) lipids, whose headgroup is most common in cell membranes, were used as model lipids. The adsorption and rupture of PC liposomes on microplastics were systematically studied. We found that divalent metal ions, such as Mg2+ and Ca2+, facilitate liposome adsorption onto microplastics and induce 40–55% liposome leakage at 2.5 mM. In contrast, to achieve a similar effect, 300 mM Na+ was required. Adsorption and rupture followed the same metal concentration requirements, suggesting that liposome adsorption was the rate-limiting step. After adsorption with liposomes, microplastics became more hydrophilic and were better dispersed in water. A similar behavior was observed for all five types of tested microplastics, including PP, PE, PVC, PET, and PS. Leakage also occurred in ocean water. This study provides fundamental insights into the interactions between liposomes and microplastics and has implications for the colloidal and transport properties of microplastics.
Salt-Toggled Capture Selection of Uric Acid Binding Aptamers
(Chemistry Europe: European Chemical Societies Publishing (ECSP), 2023-01-17) Liu, Yibo; Liu, Juewen
Uric acid is the end-product of purine metabolism in humans and an important biomarker for many diseases. To achieve the detection of uric acid without using enzymes, we previously selected a DNA aptamer for uric acid with a Kd of 1 μM but the aptamer required multiple Na+ ions for binding. Saturated binding was achieved with around 700 mM Na+ and the binding at the physiological condition was much weaker. In this work, a new selection was performed by alternating Mg2+-containing buffers with Na+ and Li+. After 13 rounds of selection, a new aptamer sequence named UA-Mg-1 was obtained. Isothermal titration calorimetry confirmed aptamer binding in both selection buffers, and the Kd was around 8 μM. The binding of UA-Mg-1 to UA required only Mg2+. This is an indicator of successful switching of metal dependency via the salt-toggled selection method. The UA-Mg-1 aptamer was engineered into a fluorescent biosensor based on the strand-displacement assay with a limit of detection of 0.5 μM uric acid in the selection buffer. Finally, comparison with the previously reported Na+-dependent aptamer and a xanthine/uric acid riboswitch was also made.
Selection of DNA Aptamers for Sensing Uric Acid in Simulated Tears
(Chemistry Europe: European Chemical Sciences Publishing, 2022-03-30) Liu, Yibo; Liu, Juewen
Uric acid is a biomarker for a range of diseases and hyperuricemia is the cause of many diseases including gout. While most biosensors for detecting uric acid relied on enzymatic reactions, in this work a library-immobilization method was used to obtain DNA aptamers for uric acid. After 18 rounds of selection, two representative aptamers were obtained with a Kd around 1.2 μM measured by isothermal titration calorimetry (ITC). Based on their difference in binding to xanthine, which differs from uric acid by only one oxygen atom, these two aptamers have different binding orientations to uric acid. ITC also indicated that the UA-1 aptamer specifically required a high concentration of Na+ for binding, which cannot be replaced by Li+, K+ or Mg2+. Combined ITC and fluorescence spectroscopy data indicated the need of three Na+ ions, which explained the requirement of a high Na+ concentration. The UA-1 aptamer was engineered into a fluorescent biosensor based on the strand-displacement reaction, resulting in a limit of detection of 90 nM uric acid. This sensor was also tested in simulated tears with a limit of detection of 350 nM uric acid.