Distribution of Copper, Iron, and Zinc in the Retina, Hippocampus, and Cortex of the Transgenic APP/PS1 Mouse Model of Alzheimer's Disease.

A mis-metabolism of transition metals (i.e., copper, iron, and zinc) in the brain has been recognised as a precursor event for aggregation of Amyloid-β plaques, a pathological hallmark of Alzheimer's disease (AD).

Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy.

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.

A Portable RT-LAMP/CRISPR Machine for Rapid COVID-19 Screening.

The COVID-19 pandemic has changed people's lives and has brought society to a sudden standstill, with lockdowns and social distancing as the preferred preventative measures. To lift these measurements and reduce society's burden, developing an easy-to-use, rapid, and portable system to detect SARS-CoV-2 is mandatory. To this end, we developed a portable and semi-automated device for SARS-CoV-2 detection based on reverse transcription loop-mediated isothermal amplification followed by a CRISPR/Cas12a reaction.

Upconversion nanoparticle-assisted single-molecule assay for detecting circulating antigens of aggressive prostate cancer.

Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single-molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo-stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican-1 (GPC-1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer.

Non-viral gene delivery utilizing RALA modulates sFlt-1 secretion, important for preeclampsia.

Overexpression of sFlt-1 or modulation of FKBPL, key antiangiogenic proteins, are important in the pathogenesis of preeclampsia. A newly developed nonviral gene-delivery system, RALA, capable of overexpressing sFlt-1 (e15a isoform) was delivered in transgenic haploinsufficient () mice. RALA was also used to deliver human Flt1 (hFlt1) in trophoblast cells.

Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.

The blood-brain barrier (BBB) is a highly specialized neurovascular unit, initially described as an intact barrier to prevent toxins, pathogens, and potentially harmful substances from entering the brain. An intact BBB is also critical for the maintenance of normal neuronal function. In cerebral vascular diseases and neurological disorders, the BBB can be disrupted, contributing to disease progression.

Stable and Highly Efficient Antibody-Nanoparticles Conjugation.

Functional ligands and polymers have frequently been used to yield target-specific bio-nanoconjugates. Herein, we provide a systematic insight into the effect of the chain length of poly(oligo (ethylene glycol) methyl ether acrylate) (POEGMEA) containing polyethylene glycol on the colloidal stability and antibody-conjugation efficiency of nanoparticles. We employed Reversible Addition-Fragmentation Chain Transfer (RAFT) to design diblock copolymers composed of 7 monoacryloxyethyl phosphate (MAEP) units and 6, 13, 35, or 55 OEGMEA units.

Blood-brain barrier-penetrating siRNA nanomedicine for Alzheimer's disease therapy.

Toxic aggregated amyloid-β accumulation is a key pathogenic event in Alzheimer's disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (β-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy.

Dispersion stability and biocompatibility of four ligand-exchanged NaYF: Yb, Er upconversion nanoparticles.

Surface modification to obtain high dispersion stability and biocompatibility is a key factor for bio-application of upconversion nanoparticles (UCNPs). A systematic study of UCNPs modified with four hydrophilic molecules separately, comparing their dispersion stability in biological buffers and cellular biocompatibility is reported here. The results show that carboxyl-functionalized UCNPs (modified by 3,4-dihydrocinnamic acid (DHCA) or poly(monoacryloxyethyl phosphate (MAEP)) with negative surface charge have superior even-distribution in biological buffers compared to amino-functionalized UCNPs (modified by (aminomethyl)phosphonic (AMPA) or (3-Aminopropyl)triethoxysilane (APTES)) with positive surface charge.

A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease.

Background: A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer's disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age.

Novel screening test for celiac disease using peptide functionalised gold nanoparticles.

Aim: To develop a screening test for celiac disease based on the coating of gold nanoparticles with a peptide sequence derived from gliadin, the protein that triggers celiac disease.

Methods: 20 nm gold nanoparticles were first coated with NeutrAvidin. A long chain Polyethylene glycol (PEG) linker containing Maleimide at the Ω-end and Biotin group at the α-end was used to ensure peptide coating to the gold nanoparticles.

Versatile multicolor nanodiamond probes for intracellular imaging and targeted labeling.

We report on the sizable production of fluorescent nanodiamonds (FNDs) containing a near infrared (NIR) color center - namely the silicon vacancy (SiV) defect, and their first demonstration inside cells for bio-imaging. We further demonstrate a concept of multi-color bio-imaging using FNDs to investigate intercellular processes using two types of FNDs. Due to their specific spectral properties, SiV FNDs can be distinguished from common nitrogen-vacancy (NV) FNDs and show a distinct initial spreading throughout the cell interior.

Stilbenes from Veratrum maackii Regel Protect against Ethanol-Induced DNA Damage in Mouse Cerebellum and Cerebral Cortex.

Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as "Lilu" and is reported to contain a family of compounds called stilbenes that can have positive biological activity.

A supramolecular self-assembly strategy for upconversion nanoparticle bioconjugation.

An efficient surface modification for upconversion nanoparticles (UCNPs) is reported via supramolecular host-guest self-assembly. Cucurbit[7]uril (CB) can provide a hydrophilic surface and cavities for most biomolecules. High biological efficiency, activity and versatility of the approach enable UCNPs to be significantly applied in bio-imaging, early disease detection, and bio-sensing.

Systematic investigation of functional ligands for colloidal stable upconversion nanoparticles.

Despite intense efforts on surface functionalization to generate hydrophilic upconversion nanoparticles (UCNPs), long-term colloidal stability in physiological buffers remains a major concern. Here we quantitatively investigate the competitive adsorption of phosphate, carboxylic acid and sulphonic acid onto the surface of UCNPs and study their binding strength to identify the best conjugation strategy. To achieve this, we designed and synthesized three di-block copolymers composed of poly(ethylene glycol) methyl ether acrylate and a polymer block bearing phosphate, carboxylic or sulphonic acid anchoring groups prepared by an advanced polymerization technique, Reversible Addition Fragmentation Chain Transfer (RAFT).

Exonuclease III-Assisted Upconversion Resonance Energy Transfer in a Wash-Free Suspension DNA Assay.

Sensitivity is the key in optical detection of low-abundant analytes, such as circulating RNA or DNA. The enzyme Exonuclease III (Exo III) is a useful tool in this regard; its ability to recycle target DNA molecules results in markedly improved detection sensitivity. Lower limits of detection may be further achieved if the detection background of autofluorescence can be removed.

Celiac disease: from etiological factors to evolving diagnostic approaches.

Celiac disease has advanced from a medical rarity to a highly prevalent disorder. Patients with the disease show varying degrees of chronic inflammation within the small intestine due to an aberrant immune response to the digestion of gliadin found in wheat. As a result, cytokines and antibodies are produced in celiac patients that can be used as specific biomarkers for developing diagnostic tests.

Robust, directed assembly of fluorescent nanodiamonds.

Arrays of fluorescent nanoparticles are highly sought after for applications in sensing, nanophotonics and quantum communications. Here we present a simple and robust method of assembling fluorescent nanodiamonds into macroscopic arrays. Remarkably, the yield of this directed assembly process is greater than 90% and the assembled patterns withstand ultra-sonication for more than three hours.

Delivery of Fluorescent Nanoparticles to the Brain.

Nanotechnology applications in neuroscience promises to deliver significant scientific and technological breakthroughs, providing answers to unresolved questions regarding the processes occurring in the brain. In this perspective, we provide a short background on two distinct fluorescent nanoparticles and summarize several studies focussed on achieving delivery of these into the brain and their interaction with brain tissue. Furthermore, we discuss challenges and opportunities for further development of nanoparticle-based therapies for targeting delivery of drugs across the blood-brain barrier.

Localization of Narrowband Single Photon Emitters in Nanodiamonds.

Diamond nanocrystals that host room temperature narrowband single photon emitters are highly sought after for applications in nanophotonics and bioimaging. However, current understanding of the origin of these emitters is extremely limited. In this work, we demonstrate that the narrowband emitters are point defects localized at extended morphological defects in individual nanodiamonds.

Facile Self-Assembly of Quantum Plasmonic Circuit Components.

A facile and cost-effective self-assembly route to engineering of vital quantum plasmonic circuit components is reported. By modifying the surface energy of silver nanowires, the position and density of attached nanodiamonds can be maneuvered leading to silver nanowire/nanodiamond(s) hybrid nanostructures. These structures exhibit strong plasmonic coupling effects and thus hold promise to serve as quantum plasmonic components.

A graphene field-effect transistor as a molecule-specific probe of DNA nucleobases.

Fast and reliable DNA sequencing is a long-standing target in biomedical research. Recent advances in graphene-based electrical sensors have demonstrated their unprecedented sensitivity to adsorbed molecules, which holds great promise for label-free DNA sequencing technology. To date, the proposed sequencing approaches rely on the ability of graphene electric devices to probe molecular-specific interactions with a graphene surface.

Enhanced photoluminescence from single nitrogen-vacancy defects in nanodiamonds coated with phenol-ionic complexes.

Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing.

Fabrication of planarised conductively patterned diamond for bio-applications.

The development of smooth, featureless surfaces for biomedical microelectronics is a challenging feat. Other than the traditional electronic materials like silicon, few microelectronic circuits can be produced with conductive features without compromising the surface topography and/or biocompatibility. Diamond is fast becoming a highly sought after biomaterial for electrical stimulation, however, its inherent surface roughness introduced by the growth process limits its applications in electronic circuitry.