Publications by authors named "Ka-Leung Wong"

Epstein-Barr nuclear antigen 1 (EBNA1), a sequence-specific DNA binding protein of Epstein-Barr virus (EBV), is essential for viral genome replication and maintenance and is therefore an attractive target for the therapeutic intervention of EBV-associated cancers. Several EBNA1-specific inhibitors have demonstrated the ability to block EBNA1 function in vitro, but practical delivery strategies for these inhibitors in vivo are still lacking. Here, we report an intelligent hierarchical targeting theranostic nanosystem (denoted as mZGOCS@MnO-P5) that integrates an azide (N3) terminal dual-targeting peptide (N3-P5), a tumor microenvironment-responsive degradable MnO nanosheet, and a mesoporous ZnGaO:Cr, Sn near-infrared persistent luminescence (NIR-PL) nanosphere (mZGOCS).

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Unlabelled: This study involves longitudinal neuro-electrophysiological analysis using motor-evoked potentials (MEP) and the Basso, Beattie, and Bresnahan behavioral examinations (BBB) to evaluate moderate mid-thoracic contusive spinal cord injury (SCI) in a rat model.

Objectives/background: The objective of the study is to characterize the onset and progression of contusive SCI over an eight-week period using a clinically applicable tool in an in vivo model. The background highlights the importance of a reliable and reproducible injury model and assessment tools for SCI.

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The conventional energy transfer pathway in organic lanthanide complexes is purported to be from the excited singlet state of the chromophore to the triplet state and subsequently directly to the emitting state of the trivalent lanthanide ion. In this work, we found that the energy transfer occurs from the triplet state to the nearest energy level, instead of directly to the emitting state of the lanthanide ion. The triplet decay rate for different lanthanide ions follows an energy gap law from the triplet level to the receiving level of the lanthanide ion.

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Upconversion nanoparticles (UCNPs) are a class of nanomaterials composed of lanthanide ions with great potential for paraclinical applications, especially in laboratory and imaging sciences. UCNPs have tunable optical properties and the ability to convert long-wavelength (low energy) excitation light into short-wavelength (high energy) emission in the ultraviolet (UV)-visible and near-infrared (NIR) spectral regions. The core-shell structure of UCNPs can be customized through chemical synthesis to meet the needs of different applications.

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Cyclen-peptide bioconjugates are usually prepared in multiple steps that require individual preparation and purification of the cyclic peptide and hydrophilic cyclen derivatives. An efficient strategy is discovered for peptide cyclization and functionalization toward lanthanide probe via three components intermolecular crosslinking on solid-phase peptide synthesis with high conversion yield. Multifunctionality can be conferred by introducing different modular parts or/and metal ions on the cyclen-embedded cyclopeptide.

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Background: SCI is a time-sensitive debilitating neurological condition without treatment options. Although the central nervous system is not programmed for effective endogenous repairs or regeneration, neuroplasticity partially compensates for the dysfunction consequences of SCI.

Objective And Hypothesis: The purpose of our study is to investigate whether early induction of hypothermia impacts neuronal tissue compensatory mechanisms.

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The efficacy of photodynamic therapy (PDT) is highly dependent on the photosensitizer features. The reactive oxygen species (ROS) generated by photosensitizers is proven to be associated with immunotherapy by triggering immunogenic cell death (ICD) as well. In this work, we establish a rhodamine-iridium(III) hybrid model functioning as a photosensitizer to comprehensively understand its performance and potential applications in photodynamic immunotherapy.

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The blood-brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics.

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Objectives: To investigate the role of urine spermine and spermine risk score in predicting prostate cancer (PCa) diagnoses in combination with multiparametric magnetic resonance imaging (mpMRI).

Methods: Three hundred forty seven consecutive men with elevated prostate-specific antigen (PSA) with mpMRI examination were prospectively enrolled in this study. In 265 patients with PSA levels between 4 and20 ng/ml, pre-biopsy urine samples were analyzed for spermine levels with ultra-high performance liquid chromatography (UPLC-MS/MS).

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Undoped YTiO exhibits impurity emission bands at low temperatures due to Mn and Cr, as established by codoping with these ions. Contrary to a recent report by Wang et al., , , 36834-36844, we do not observe Bi emission in this codoped host, as also is the case for Fe.

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The responsive control of energy transfer (ET) plays a key role in the broad applications of lanthanide-doped nanomaterials. Photonic crystals (PCs) are excellent materials for ET regulation. Among the numerous materials that can be used to fabricate PCs, chiral nematic liquid crystals are highly attractive due to their good photoelectric responsiveness and biocompatibility.

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Corroles have attracted increasing research interests in recent decades owing to their unique properties over porphyrins. However, the relatively inefficient and tedious synthetic procedures of corrole building blocks with functional groups for bioconjugation hindered their bioapplications. Herein, we report a highly efficient protocol to synthesize corrole-peptide conjugates with good yields (up to 63 %) without using prepared corrole building blocks.

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Nasopharyngeal carcinoma (NPC) is a diverse cancer with no well-defined tumor antigen, associated with oncogenic Epstein-Barr Virus (EBV), and with usually late-stage diagnosis and survival <40%. Current radiotherapy and chemotherapy have low effectiveness and cause adverse effects, which calls for the need of new therapy. In this regard, adoptive immunotherapy using γδ T cells has potential, but needs to be coupled with butyrophilin 2A1 and 3A1 protein expression to achieve tumoricidal effect.

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The excitation energy transfer (ET) pathway and mechanism from an organic antenna to a lanthanide ion has been the subject of discussion for many decades. In the case of europium (Eu), it has been suggested that the transfer originates from the ligand singlet state or a triplet state. Taking the lanthanide complex as an example, we have investigated the spectra and luminescence kinetics, mainly at room temperature and 77 K, to acquire the necessary experimental data.

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Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency.

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Epstein-Barr virus (EBV) is a common human-infected virus related to many diseases and cancers. Recently, some peptides have been found to serve targeting and therapeutic roles by inhibiting EBNA1, an oncoprotein of the EBV. We herein report the conjugation of the EBNA1-targeting peptides and porphyrins which can bring synergistic effects by both introducing more specific treatments (photodynamic therapy) and improving the biocompatibility of the photosensitizer and the peptides.

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We have prepared a hetero-tetrametallic assembly consisting of three ytterbium ions coordinated to a central [Ru(bpm)] (bpm = 2,2'-bipyrimidine) motif. Irradiation into the absorption band of the peripheral ytterbium ions at 980 nm engenders emission of the MLCT state of the central [Ru(bpm)] core at 636 nm, which represents the first example of f → d molecular upconversion (UC). Time-resolved measurements reveal a slow rise of the UC emission, which was modeled with a mathematical treatment of the observed kinetics according to a cooperative photosensitization mechanism using a virtual Yb centered doubly excited state followed by energy transfer to the Ru centered MLCT state.

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Multifunctional porphyrin-peptide conjugates with different propensities for self-assembly into various supramolecular nanoarchitectures play important roles in advanced materials and biomedical research. However, preparing prefunctionalized core porphyrins by traditional low-yielding statistical synthesis and purifying them after peptide ligation through many rounds of HPLC purification is tedious and unsustainable. Herein, we report a novel integrated solid-phase synthetic protocol for the construction of porphyrin moieties from simple aldehydes and dipyrromethanes on resin-bound peptides directly to form mono-, cis/trans-di-, and trivalent porphyrin-peptide conjugates in a highly efficient and controllable manner; moreover, only single final-stage HPLC purification of the products is needed.

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The effect of temperature upon the lanthanide luminescence lifetime and intensity has been investigated in toluene solution for the complexes (Ln = Eu, Sm, Nd, Yb; Phen = 1,10-phenanthroline; TTA = thenoyltrifluoroacetonate). Thermally excited back-transfer to a charge transfer state was found to occur for Ln = Eu and can be explained by lifetime and intensity back-transfer models. The emission intensity and lifetime were also quenched with increasing temperature for Ln = Sm, and the activation energy for nonradiative decay is similar to that for the thermal population of Sm excited states.

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Correction for 'Incorporation of Fmoc-Dab(Mtt)-OH during solid-phase peptide synthesis: a word of caution' by Pak-Lun Lam , , 2022, DOI: 10.1039/d2ob00070a.

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As a commercially available and orthogonally protected amino acid building block, Fmoc-Dab(Mtt)-OH showed abnormally poor coupling efficiency during solid-phase peptide synthesis (SPPS). Herein, we reveal that Fmoc-Dab(Mtt)-OH undergoes rapid lactamization under a series of conditions with various coupling reagents. Although the complete incorporation of Fmoc-Dab(Mtt)-OH can be achieved using a multi-time and preincubation-free protocol with the coupling reagent DEPBT, alternative orthogonally protected building blocks are suggested to be used for avoiding such a costly and tedious procedure.

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Intravenous delivery of nanomaterials containing therapeutic agents and various cargos for treating neurological disorders is often constrained by low delivery efficacy due to difficulties in passing the blood-brain barrier (BBB). Nanoparticles (NPs) administered intranasally can move along olfactory and trigeminal nerves so that they do not need to pass through the BBB, allowing non-invasive, direct access to selective neural pathways within the brain. Hence, intranasal (IN) administration of NPs can effectively deliver drugs and genes into targeted regions of the brain, holding potential for efficacious disease treatment in the central nervous system (CNS).

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Hybrid upconversion nanosystems have been reported to improve the low absorption efficiency of lanthanide-doped upconversion nanoparticles (UCNPs). However, the low quantum yield and poor photostability of NIR dyes pose challenges for practical uses. Here, we introduce a bulky moiety, 4-(1,2,2-triphenylvinyl)-1,1'-biphenyl (TPEO), to enhance its quantum yield by suppressing the bond rotation and improve the stability by deactivating the photoinduced oxidization.

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Emission from the triplet state of an organo-lanthanide complex is observed only when the energy transfer to the lanthanide ion is absent. The triplet state lifetime under cryogenic conditions for organo-lanthanide compounds usually ranges up to tens of milliseconds. The compound LaL1(TTA) reported herein exhibits 77 K phosphorescence observable by the naked eye for up to 30 s.

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