A CRISPR-Cas12a-mediated dual-mode luminescence and colorimetric nucleic acid biosensing platform based on upconversion nanozyme.

In this study, a CRISPR-Cas12a-mediated dual-mode upconversion luminescence/colorimetric nucleic acid biosensing platform is developed based on UCNP@SiO/CeO (UNSC) nanozyme. Here, UNSC is conjugated with single-stranded DNA (ssDNA) probes used as both peroxidase-like nanozyme and upconversion luminescence donors. When no target nucleic acid is present, ssDNA-conjugated UNSC attaches on magnetic graphene oxide (MGO) via pi-pi stacking force, resulting in upconversion luminescence quenching (OFF) and no color change after magnetic removal of nanozymes attached on the MGO.

Tau‑targeting multifunctional nanocomposite based on tannic acid-metal for near-infrared fluorescence/magnetic resonance bimodal imaging-guided combinational therapy in Alzheimer's disease.

Alzheimer's disease (AD) is hallmarked by amyloid-β (Aβ) plaques and hyperphosphorylated tau (p-tau) neurofibrillary tangles. While Aβ-centric therapies have shown promise, the complex pathology of AD requires a multifaceted therapeutic approach. The weak association between Aβ levels and cognitive decline highlights the need for alternative theranostic strategies.

A smartphone-assisted electrochemiluminescent biosensor for highly sensitive detection of miRNA-21 based on Ru(bpy)(L)@MOF-5.

A smartphone-assisted electrochemiluminescence (ECL) strategy based on Ru(bpy)(L) as chromophores confined with metal - organic frameworks (Ru(bpy)(L)@MOF-5) for the signal-amplified detection of miRNA-21 was developed. We synthesized a derivative of tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)(L)) with high charges, which can be loaded into the MOF-5 by strong electrostatic interaction to prevent from leakage. In addition, nucleic acid cycle amplification was used to quench the signal of Ru(bpy)(L)@MOF-5 by ferrocene.

Synthesis of a metal-organic framework Cu-Mi-UiO-66-based fluorescent nanoprobe for the simultaneous sensing and intracellular imaging of GSH and ATP.

This study reports a fluorescent nanoprobe operated in fluorescence turn-on mode for simultaneously sensing and imaging intracellular GSH and ATP. By using maleimide-derivatives as the ligand, the bimetallic nanoscale metal-organic framework (NMOF) Cu-Mi-UiO-66 has been synthesized for the first time using a straightforward one-step solvothermal approach, serving as a GSH recognition moiety. Subsequently, a Cy5-labeled ATP aptamer was assembled onto Cu-Mi-UiO-66 strong coordination between phosphate and zirconium, π-π stacking and electrostatic adsorption to develop the dual-responsive fluorescence nanoprobe Cu-Mi-UiO-66/aptamer.

Magnetic-responsive upconversion luminescence resonance energy transfer (LRET) biosensor for ultrasensitive detection of SARS-CoV-2 spike protein.

Upconversion nanoparticles (UCNPs) are ideal donors for luminescence resonance energy transfer (LRET)-based biosensors due to their excellent upconversion luminescence properties. However, the relatively large size of antibodies and proteins limits the application of UCNPs-based LRET biosensors in protein detection because the large steric hindrance of proteins leads to low energy transfer efficiency between UCNPs and receptors. Herein, we developed a magnetic responsive UCNPs-based LRET biosensor to control the coupling distance between antibody-functionalized UCNPs (Ab-UCNPs) as donors and antibody-PEG linker-magnetic gold nanoparticles (Ab-PEG-MGNs) as acceptors for ultrasensitive and highly selective detection of SARS-CoV-2 spike proteins.

Development of enzyme-inorganic hybrid nanoflower-modified electrodes and a smartphone-controlled electrochemical analyzer for point-of-care testing of salivary amylase in saliva.

Quantitation of salivary alpha-amylase (sAA) plays a significant role in not only theoretical studies but also clinical practice. This study reports a quantitative point-of-care testing (POCT) system for sAA quantitation anywhere, anytime and by anyone, which consists of customized electrodes and a smartphone-controlled electrochemical analyzer. Organic-inorganic hybrid nanoflowers (NFs) encapsulating α-glucosidase (AG) and glucose dehydrogenase (GDH) have been synthesized and modified onto screen-printed electrodes (SPCEs) to fabricate the customized electrodes.

A smartphone-assisted electrochemiluminescent detection of miRNA-21 in situ using Ru(bpy)@MOF.

We have proposed a signal dual-amplification electrochemiluminescence (ECL) strategy based on tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)) as chromophores confined with three-dimensional (3D) zinc oxalate metal-organic frameworks (Ru(bpy)@MOFs) for the detection of miRNA-21. The three-dimensional chromophore connectivity in zinc oxalate MOFs provided a network among Ru(bpy) units, shielding the chromophores from solvent molecules and resulting in high Ru(II) complex emission efficiency. Additionally, we discovered that magnetic beads (MBs) used as carrier for enriched signals contribute to enhanced ECL intensity of the chromophore.

On-site quantitation of xanthine in fish and serum using a smartphone-based spectrophotometer integrated with a dual-readout nanosensing assay.

Rapid and quantitative biochemical analysis at points-of-need is imperative for food safety inspection. This work reports on: 1) a stand-alone smartphone-based "two-in-one" spectrophotometer (the SAFS) installed with a self-developed application (the SAFS-App) which can precisely collect both absorption spectra and fluorescence spectra in a reproducible manner within 5 s; and 2) a straightforward protocol for xanthine detection using fluorescent carbon nanodots and silver nanoparticles. The assay performed with the SAFS demonstrates high specificity towards xanthine, and a linear range of 1-60 μM with LODs of 0.

An MMP-2 Responsive Nanotheranostic Probe Enabled Synergistic Therapy of Rheumatoid Arthritis and MR/CT Assessment of Therapeutic Response In Situ.

This study reports a facile and green synthesis of a new multifunctional nanotheranostic probe for the synergistic therapy of rheumatoid arthritis (RA) and in situ assessment of therapeutic response. The probe is synthesized through a one-step self-assembly of two exquisitely designed peptide-amphiphilic block copolymers (PEG-DTIPA-KGPLGVRK-MTX and Pal-GGGGHHHHD-TCZ) under mild conditions, requiring minimal energy input. The resultant probe demonstrates excellent biocompatibility, water solubility, and colloidal stability.

A smartphone-based fluorospectrophotometer and ratiometric fluorescence nanoprobe for on-site quantitation of pesticide residue.

Cost-effective and user-friendly quantitation at points-of-need plays an important role in food safety inspection, environmental monitoring, and biomedical analysis. This study reports a stand-alone smartphone-based fluorospectrophotometer (the SBS) installed with a custom-designed application (the SBS-App) for on-site quantitation of pesticide using a ratiometric sensing scheme. The SBS can collect fluorescence emission spectra in the wavelength range of 380-760 nm within 5 s.

3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor-on-a-Chip.

Decades of efforts in engineering in vitro cancer models have advanced drug discovery and the insight into cancer biology. However, the establishment of preclinical models that enable fully recapitulating the tumor microenvironment remains challenging owing to its intrinsic complexity. Recent progress in engineering techniques has allowed the development of a new generation of in vitro preclinical models that can recreate complex in vivo tumor microenvironments and accurately predict drug responses, including spheroids, organoids, and tumor-on-a-chip.

Development of Smartphone-Controlled and Microneedle-Based Wearable Continuous Glucose Monitoring System for Home-Care Diabetes Management.

Continuous glucose monitoring (CGM) can mini-invasively track blood glucose fluctuation and reduce the risk of hyperglycemia and hypoglycemia, and this is is in great demand for diabetes management. However, cost-effective manufacture of CGM systems with continuously improved convenience and performance is still the persistent goal. Herein, we developed a smartphone-controlled and microneedle (MN)-based wearable CGM system for long-term glucose monitoring.

BSA-templated synthesis of Ir/Gd bimetallic oxide nanotheranostics for MR/CT imaging-guided photothermal and photodynamic synergistic therapy.

Precision medicine urges the development of theranostics which can efficiently integrate precise diagnosis and effective therapy. In this study, a facile synthesis of Ir/Gd bimetallic oxide nanotheranostics (termed BSA@GdO/IrO NPs) with good biocompatibility was demonstrated using a biomineralization method where bovine serum albumin (BSA) served as a versatile template. BSA@GdO/IrO NPs exhibited high longitudinal relaxivity (5.

Near-Infrared Photothermally Enhanced Photo-Oxygenation for Inhibition of Amyloid-β Aggregation Based on RVG-Conjugated Porphyrinic Metal-Organic Framework and Indocyanine Green Nanoplatform.

Amyloid aggregation is associated with many neurodegenerative diseases such as Alzheimer's disease (AD). The current technologies using phototherapy for amyloid inhibition are usually photodynamic approaches based on evidence that reactive oxygen species can inhibit Aβ aggregation. Herein, we report a novel combinational photothermally assisted photo-oxygenation treatment based on a nano-platform of the brain-targeting peptide RVG conjugated with the 2D porphyrinic PCN-222 metal-organic framework and indocyanine green (PCN-222@ICG@RVG) with enhanced photo-inhibition in Alzheimer's Aβ aggregation.

Fluorescent on-site detection of multiple pathogens using smartphone-based portable device with paper-based isothermal amplification chip.

The development of cost-effective, portable, and ease-of-use sensing system for on-site genetic diagnostics is highly desirable for pathogen screening and infectious disease diagnosis. This study develops (1) a paper-based biochip which is able to integrate the loop-mediated isothermal amplification (LAMP) protocols for simultaneous detection of Escherichia coli O157:H7, Salmonella spp., and Staphylococcus aureus, and (2) a stand-alone smartphone-based portable device which can control exactly 65 °C for isothermal amplification as well as collect and analyze the thus generated fluorescence signals.

A CRISPR-Cas12a integrated SERS nanoplatform with chimeric DNA/RNA hairpin guide for ultrasensitive nucleic acid detection.

CRISPR-Cas12a has been integrated with nanomaterial-based optical techniques, such as surface-enhanced Raman scattering (SERS), to formulate a powerful amplification-free nucleic acid detection system. However, nanomaterials impose steric hindrance to limit the accessibility of CRISPR-Cas12a to the narrow gaps (SERS hot spots) among nanoparticles (NPs) for producing a significant change in signals after nucleic acid detection. To overcome this restriction, we specifically design chimeric DNA/RNA hairpins (displacers) that can be destabilized by activated CRISPR-Cas12a in the presence of target DNA, liberating excessive RNA that can disintegrate a core-satellite nanocluster via toehold-mediated strand displacement for orchestrating a promising "on-off" nucleic acid biosensor.

An AIEgen/graphene oxide nanocomposite (AIEgen@GO)-based two-stage "turn-on" nucleic acid biosensor for rapid detection of SARS-CoV-2 viral sequence.

The ongoing outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has posed significant challenges in early viral diagnosis. Hence, it is urgently desirable to develop a rapid, inexpensive, and sensitive method to aid point-of-care SARS-CoV-2 detection. In this work, we report a highly sequence-specific biosensor based on nanocomposites with aggregation-induced emission luminogens (AIEgen)-labeled oligonucleotide probes on graphene oxide nanosheets (AIEgen@GO) for one step-detection of SARS-CoV-2-specific nucleic acid sequences ( or genes).

Virus Detection: From State-of-the-Art Laboratories to Smartphone-Based Point-of-Care Testing.

Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers.

A touch-actuated glucose sensor fully integrated with microneedle array and reverse iontophoresis for diabetes monitoring.

The development of non-invasive biosensor for monitoring glucose in interstitial fluid (ISF) is still challenging, because ISF extraction through classical reverse iontophoresis (RI) is limited by low extraction flux and consistency. Here, we developed a touch-actuated biosensor for monitoring glucose in ISF. The biosensor is composed of three main components: 1) the solid microneedle array (MA) for painless skin penetration; 2) the RI unit for ISF extraction through the MA-created microchannels; and 3) the sensing unit for glucose monitoring.

Recent Progress in Microneedles-Mediated Diagnosis, Therapy, and Theranostic Systems.

Theranostic system combined diagnostic and therapeutic modalities is critical for the real-time monitoring of disease-related biomarkers and personalized therapy. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. They have shown attractive properties including painless skin penetration, easy self-administration, prominent therapeutic effects, and good biosafety.

Hybrid theranostic microbubbles for ultrasound/photoacoustic imaging guided starvation/low-temperature photothermal/hypoxia-activated synergistic cancer therapy.

Constructing a theranostic agent for high-contrast multimodality imaging-guided synergistic therapy with long-term tumor retention and minimum systemic side effects still remains a major challenge. Herein, a hybrid microbubble-based theranostic platform was developed for dual-modality ultrasound (US) and enhanced photoacoustic (PA) imaging-guided synergistic tumor therapy by combining starvation therapy, low-temperature photothermal therapy (PTT), and hypoxia-activated therapy, based on polydopamine (PDA) doped poly(vinyl alcohol) microbubbles loaded with glucose oxidase (GOx) (PDA-PVAMBs@GOx) and hypoxia-activated prodrug (HAP) tirapazamine (TPZ). For dual-modality US/enhanced PA imaging, PDA-PVAMBs provided 6.

Development of gold nanoparticles-aptamer nanocomposite for multiplexed analysis of antibiotics and design of molecular logic gates.

The widespread use of antibiotics caused severe problems of antibiotic residues in foodstuffs and water, posing a serious threat to public health and thus urging the development of sensitive, selective, and rapid detection methods for antibiotics. In this study, a fluorescence resonance energy transfer (FRET)-based system is developed for the multiplexed analysis of chloramphenicol (CAP) and streptomycin (Strep) with detection limits of 2.51 and 8.

Gadolinium-porphyrin based polymer nanotheranostics for fluorescence/magnetic resonance imaging guided photodynamic therapy.

Nanotheranostics for fluorescence/magnetic resonance (FL/MR) dual-modal imaging guided photodynamic therapy (PDT) are highly desirable in precision and personalized medicine. In this study, a facile non-covalent electrostatic interaction induced self-assembly strategy is developed to effectively encapsulate gadolinium porphyrin (Gd-TCPP) into homogeneous supramolecular nanoparticles (referred to as Gd-PNPs). Gd-PNPs exhibit the following advantages: (1) excellent FL imaging property, high longitudinal relaxivity (16.