Enzyme-Activated Orthogonal Proteolysis Chimeras for Tumor Microenvironment-Responsive Immunomodulation.

Precise modulation of dynamic and complex tumor microenvironment (TME) to disrupt tumorigenesis and reshape intratumoral immune infiltration has emerged as promising approaches for enhanced cancer therapy. Among recent innovations, proteolysis-targeting chimeras (PROTACs) represent a burgeoning chemical knockdown technology capable of degrading oncogenic protein homeostasis and inducing dynamic alternations within carcinoma settings, offering potential for antitumor manipulation. However, achieving selectivity in PROTACs that respond to disease environmental stimulation and precisely perturb on-target proteins remains challenging.

Harnessing from Nature - Evolving Potential of Antimicrobial Peptide.

Antimicrobial peptides (AMPs) are recognized as one of the most ancient components of innate immunity, playing a pivotal role as the first line of host defense systems. These evolutionarily conserved molecules have been identified in various organisms, from prokaryotes to humans. AMPs establish a delicate balanced relationship between host and microbes, by simultaneously regulating the biological activities of pathogens and commensal microbes.

A Nitroreductase-Activatable Metabolic Reporter for Covalent Labeling of Pathological Hypoxic Cells in Tumorigenesis.

Aberrant hypoxic stress will initiate a cascade of pathological consequence observed prominently in tumorigenesis. Understanding of hypoxia's role in tumorigenesis is highly essential for developing effective therapeutics, which necessitates reliable tools to specifically distinguish hypoxic tumor cells (or tissues) and correlate their dynamics with the status of disease in complex living settings for precise theranostics. So far, disparate hypoxia-responsive probe molecules and prodrugs were designed via chemical or enzymatic reactions, yet their capability in real-time reporting pathogenesis development is often compromised due to unrestricted diffusion and less selectivity towards the environmental responsiveness.

Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential.

Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers.

Enzymes in Synergy: Bacteria Specific Molecular Probe for Locoregional Imaging of Urinary Tract Infection in vivo.

Uropathogenic Escherichia coli (UPECs) is a leading cause for urinary tract infections (UTI), accounting for 70-90 % of community or hospital-acquired bacterial infections owing to high recurrence, imprecision in diagnosis and management, and increasing prevalence of antibiotic resistance. Current methods for clinical UPECs detection still rely on labor-intensive urine cultures that impede rapid and accurate diagnosis for timely UTI therapeutic management. Herein, we developed a first-in-class near-infrared (NIR) UPECs fluorescent probe (NO-AH) capable of specifically targeting UPECs through its collaborative response to bacterial enzymes, enabling locoregional imaging of UTIs both in vitro and in vivo.

Beyond the TPP "gold standard": a new generation mitochondrial delivery vector based on extended PN frameworks.

Mitochondrial targeting represents an attractive strategy for treating metabolic, degenerative and hyperproliferative diseases, since this organelle plays key roles in essential cellular functions. Triphenylphosphonium (TPP) moieties - the current "gold standard" - have been widely used as mitochondrial targeting vectors for a wide range of molecular cargo. Recently, further optimisation of the TPP platform drew considerable interest as a way to enhance mitochondrial therapies.

Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria.

The emergence of multi-drug resistant bacteria strains has been an uphill battle in modern healthcare worldwide, due to the increasing difficulty of killing them. The evolving pathogenicity of bacteria has led to researchers searching for more effective antimicrobial therapeutics to successfully eliminate them without undesirable consequences to the human body. In recent years, antimicrobial photodynamic therapy (APDT), an obsolete technique for cancer treatments, has been reported to eradicate bacteria and biofilm-related infections.

Nanoparticles-mediated ion channels manipulation: From their membrane interactions to bioapplications.

Ion channels are transmembrane proteins ubiquitously expressed in all cells that control various ions (e.g. Na, K, Ca and Cl etc) crossing cellular plasma membrane, which play critical roles in physiological processes including regulating signal transduction, cell proliferation as well as excitatory cell excitation and conduction.

Near Infrared-II Photothermal and Colorimetric Synergistic Sensing for Intelligent Onsite Dietary Myrosinase Profiling.

Myrosinase (Myr) is a type of critical β-thioglucosidase enzyme activator essential for sustaining many functional foods to perform their health-promoting functions. An accurate and reliable Myr test is meaningful for food quality and dietary nutrition assessments, whereas the currently reported methods do not guarantee specificity and have high reliance on instrumentation, which are not suitable for rapid and onsite Myr screening especially in complex systems from various sources. Herein, we present a unique NIR-II absorption-based photothermal-responsive colorimetric biosensor for anti-interference onsite Myr determination and realization of rapid visualized outputs with the aid of smartphone calculation.

Highly Stretchable, Swelling-Resistant, Self-Healed, and Biocompatible Dual-Reinforced Double Polymer Network Hydrogels.

Superior flexibility and toughness can be achieved in bioactive hydrogels by the use of a double polymer network with complementary properties. Inspired by this design principle, we here combine polyacrylic acid (PAA) and sodium alginate (SA) to obtain a dual-reinforced double interpenetrating network (d-DIPN) hydrogel. The dual reinforcement involves ionic cross-linking and introduction of SiO nanoparticles, which leads to extraordinary improvements in strength and toughness.

Hypoxia deactivates epigenetic feedbacks via enzyme-derived clicking proteolysis-targeting chimeras.

Epigenetic mediation through bromodomain and extraterminal (BET) proteins have progressively translated protein imbalance into effective cancer treatment. Perturbation of druggable BET proteins through proteolysis-targeting chimeras (PROTACs) has recently contributed to the discovery of effective therapeutics. Unfortunately, precise and microenvironment-activatable BET protein degradation content with promising tumor selectivity and pharmacological suitability remains elusive.

Screening, Expression, and Identification of Nanobody against SARS-CoV-2 Spike Protein.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an infectious disease that has become a serious burden on global public health. This study screened and yielded specific nanobodies (Nbs) against SARS-CoV-2 spike protein receptor binding domain (RBD), following testing its basic characteristics. A nanobody phage library was established by immunizing a camel with RBD protein.

Detection of Reactive Oxygen and Nitrogen Species by Upconversion Nanoparticle-Based Near-Infrared Nanoprobes: Recent Progress and Perspectives.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are essential oxidative metabolites of organisms, which are closely related to physiological, pathological and pharmacological processes. The accurate detection of ROS/RNS is important for the understanding of biological processes, monitoring of pharmacological effects, and predicting the course of disease. The recently developed NIR nanoprobes based on upconversion nanoparticles (UCNPs) hold great prospects in sensitive and deep-tissue detection of ROS/RNS, and considerable progress has been achieved so far.

Resolving the Conflict between Strength and Toughness in Bioactive Silica-Polymer Hybrid Materials.

Simultaneously improving the strength and toughness of materials is a major challenge. Inorganic-polymer hybrids offer the potential to combine mechanical properties of a stiff inorganic glass with a flexible organic polymer. However, the toughening mechanism at the atomic scale remains largely unknown.

Screening of multifunctional fruit carbon dots for fluorescent labeling and sensing in living immune cells and zebrafishes.

Nine kinds of carbon dots (CDs) were synthesized by using fruits with different varieties as carbon sources; meanwhile, the fluorescence characteristics, quantum yield, and response ability to different metal ions and free radicals were systematically studied. These CDs showed similar excitation and emission spectral ranges (λ ≈ 345 nm, λ ≈ 435 nm), but very different fluorescence quantum yield (QY), in which orange and cantaloupe CDs have the highest QY around 0.25 and green plum CDs showed the lowest quantum yield around 0.

A tumor microenvironment-responsive Co/ZIF-8/ICG/Pt nanoplatform for chemodynamic and enhanced photodynamic antitumor therapy.

Hypoxia and the overexpression of hydrogen peroxide (HO) in the tumor microenvironment (TME) are conducive to cancer cell proliferation, which greatly hinders cancer treatment. Here, we design a novel TME-responsive therapeutic nanoplatform Co/ZIF-8/ICG/Pt (CZIP) to achieve chemodynamic therapy (CDT) and enhanced photodynamic therapy (PDT). In this nanoplatform, under near-infrared light (NIR) irradiation, the photosensitizer indocyanine green (ICG) can generate singlet oxygen (O) for cancer cell apoptosis.

Protein-Mediated Fluorescence Resonance Energy Transfer (P-FRET) Probe: Fabrication and Hydroxyl Radical Detection.

Fluorescent probes based on fluorescence resonance energy transfer (FRET) are highly promising for diverse bioapplications. The key to constructing FRET probes is to confine the donor and acceptor within a sufficiently close distance. However, the commonly used covalent linkage often requires elaborate design and complex organic synthesis, and sometimes causes changes in the fluorescence properties of the donor and acceptor.

Scratching the Surface of Unventured Possibilities with In Situ Self-Assembly: Protease-Activated Developments for Imaging and Therapy.

In situ self-assembly has attracted increasing research interest for applications in imaging and therapy in recent years. Particularly for protease-activated developments, inspiration is drawn from the innate specificity of their catalytic activities, rapid discovery of the various roles they play in the proliferation of certain diseases, and inherent susceptibility of small molecule peptide conjugates to proteolytic digestion in vivo. The overexpression of a disease-related protease of interest can be exploited as an endogenous stimulus for site-specific self-assembly to largely amplify a molecular event happening at the cellular level.

Near-Infrared Light Brightens Bacterial Disinfection: Recent Progress and Perspectives.

Bacterial infection is a universal threat to public health, which not only causes many serious diseases but also exacerbates the condition of the patients of cancer, pandemic diseases, , COVID-19, and so on. Antibiotic therapy has been used to be an effective way for common bacterial disinfection. However, due to the misuse and abuse of antibiotics, more and more antibiotic-resistant bacteria have emerged as fatal threats to human beings.

Tumour enzyme affinity mediated peptide molecular crowding for targeted disruption of hyperactivated glucose uptake.

An unconventional environment-responsive molecular crowding specific binding between small molecule peptide inhibitor derivatives and an overexpressed tumour enzyme has been developed. Assemblies of such short peptides selectively localize on tumour surfaces and exhibited unique functions in disrupting hyperactivated glucose uptake, providing novel insights towards strategic tumour treatment.

Alkyl aryl modifications: a comparative study on modular modifications of triphenylphosphonium mitochondrial vectors.

Triphenylphosphonium (TPP) moieties are commonly conjugated to drug molecules to confer mitochondrial selectivity due to their positive charge and high lipophilicity. Although optimisation of lipophilicity can be achieved by modifying the length of the alkyl linkers between the TPP moiety and the drug molecule, it is not always possible. While methylation of the TPP moiety is a viable alternative to increase lipophilicity and mitochondrial accumulation, there are no studies comparing these two separate modular approaches.

Small-molecule fluorescent probes: big future for specific bacterial labeling and infection detection.

Bacterial infections remain a global healthcare problem that is particularly attributed to the spread of antibiotic resistance and the evolving pathogenicity. Accurate and swift approaches for infection diagnosis are urgently needed to facilitate antibiotic stewardship and effective medical treatment. Direct optical imaging for specific bacterial labeling and infection detection offers an attractive prospect of precisely monitoring the infectious disease status and therapeutic response in real time.

Diazapentabenzocorannulenium: A Hydrophilic/Biophilic Cationic Buckybowl.

Polycyclic aromatic molecules are promising functional materials for a wide range of applications, especially in organic electronics. However, their largely hydrophobic nature has impeded further applications. As such, imparting high solubility/hydrophilicity to polycyclic aromatic molecules leads to a breakthrough in this research field.