The possibilities of LOXL4 as a prognostic marker for carcinomas.

Lysyl oxidase-like 4 (LOXL4), a member of lysyl oxidase family, is a copper and lysine tyrosylquinone-dependent amine oxidase that serves the role of catalyzing the cross-linking of elastin and collagen in the extracellular matrix. Numerous studies have shown a significant association between LOXL4 expression levels and tumor proliferation, migration, invasion and patients' prognosis and overall survival in different types of tumors. Here we review their relationship and the molecular pathogenesis behind them, aiming to explore the possibilities of LOXL4 as a prognostic marker for diverse carcinomas and provide some indications for further research in this field.

Antibacterial, antiviral, and biodegradable collagen network mask for effective particulate removal and wireless breath monitoring.

Functional face masks that can effectively remove particulate matter and pathogens are critical to addressing the urgent health needs arising from industrial air pollution and the COVID-19 pandemic. However, most commercial masks are manufactured by tedious and complicated network-forming procedures (e.g., meltblowing and electrospinning). In addition, the materials used (e.g., polypropylene) have significant limitations such as a lack of pathogen inactivation and degradability, which can cause secondary infection and serious environmental concerns if discarded. Here, we present a facile and straightforward method for creating biodegradable and self-disinfecting masks based on collagen fiber networks. These masks not only provide superior protection against a wide range of hazardous substances in polluted air, but also address environmental concerns associated with waste disposal. Importantly, collagen fiber networks with naturally existing hierarchical microporous structures can be easily modified by tannic acid to improve its mechanical characteristics and enable the in situ production of silver nanoparticles. The resulting masks exhibit excellent antibacterial (>99.99%, 15 min) and antiviral (>99.999%, 15 min) capabilities, as well as high PM2.5 removal efficiency (>99.9%, 30 s). We further demonstrate the integration of the mask into a wireless platform for respiratory monitoring. Therefore, the smart mask has enormous promise for combating air pollution and contagious viruses, managing personal health, and alleviating waste issues caused by commercial masks.

Dynamic Metal-Phenolic Coordination Complexes for Versatile Surface Nanopatterning.

We report a general nanopatterning strategy that takes advantage of the dynamic coordination bonds between polyphenols and metal ions (e.g., Fe3+ and Cu2+) to create structures on surfaces with a range of properties. With this methodology, under acidic conditions, 29 metal-phenolic complex-based precursors composed of different polyphenols and metal ions are patterned using scanning probe and large-area cantilever free nanolithography techniques, resulting in a library of deposited metal-phenolic nanopatterns. Significantly, post-treatment of the patterns under basic conditions (i.e., ammonia vapor) triggers a change in coordination state and results in the in situ generation of more stable networks firmly attached to the underlying substrates. The methodology provides control over feature size, shape, and composition, almost regardless of substrate (e.g., Si, Au, and silicon nitride). Under reducing conditions (i.e., H2) at elevated temperatures (180-600 °C), the patterned features have been used as nanoreactors to synthesize individual metal nanoparticles. At room temperature, the ammonia-treated features can reduce Ag+ to form metal nanostructures and be modified with peptides, proteins, and thiolated DNA via Michael addition and/or Schiff base reaction. The generality of this technique should make it useful for a wide variety of researchers interested in modifying surfaces for catalytic, chemical and biological sensing, and template-directed assembly purposes.

Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators.

Small-molecular Toll-like receptor 7/8 (TLR7/8) agonists hold promise as immune modulators for a variety of immune therapeutic purposes including cancer therapy or vaccination. However, due to their rapid systemic distribution causing difficult-to-control inflammatory off-target effects, their application is still problematic, in particular systemically. To address this problem, we designed and robustly fabricated pH-responsive nanogels serving as versatile immunodrug nanocarriers for safe delivery of TLR7/8-stimulating imidazoquinolines after intravenous administration. To this aim, a primary amine-reactive methacrylamide monomer bearing a pendant squaric ester amide is introduced, which is polymerized under controlled RAFT polymerization conditions. Corresponding PEG-derived squaric ester amide block copolymers self-assemble into precursor micelles in polar protic solvents. Their cores are amine-reactive and can sequentially be transformed by acid-sensitive cross-linkers, dyes, and imidazoquinolines. Remaining squaric ester amides are hydrophilized affording fully hydrophilic nanogels with profound stability in human plasma but stimuli-responsive degradation upon exposure to endolysosomal pH conditions. The immunomodulatory behavior of the imidazoquinolines alone or conjugated to the nanogels was demonstrated by macrophages in vitro. In vivo, however, we observed a remarkable impact of the nanogel: After intravenous injection, a spatially controlled immunostimulatory activity was evident in the spleen, whereas systemic off-target inflammatory responses triggered by the small-molecular imidazoquinoline analogue were absent. These findings underline the potential of squaric ester-based, pH-degradable nanogels as a promising platform to permit intravenous administration routes of small-molecular TLR7/8 agonists and, thus, the opportunity to explore their adjuvant potency for systemic vaccination or cancer immunotherapy purposes.

Precision Anisotropic Brush Polymers by Sequence Controlled Chemistry.

The programming of nanomaterials at molecular length-scales to control architecture and function represents a pinnacle in soft materials synthesis. Although elusive in synthetic materials, Nature has evolutionarily refined macromolecular synthesis with perfect atomic resolution across three-dimensional space that serves specific functions. We show that biomolecules, specifically proteins, provide an intrinsic macromolecular backbone for the construction of anisotropic brush polymers with monodisperse lengths via grafting-from strategy. Using human serum albumin as a model, its sequence was exploited to chemically transform a single cysteine, such that the expression of said functionality is asymmetrically placed along the backbone of the eventual brush polymer. This positional monofunctionalization strategy was connected with biotin-streptavidin interactions to demonstrate the capabilities for site-specific self-assembly to create higher ordered architectures. Supported by systematic experimental and computational studies, we envisioned that this macromolecular platform provides unique avenues and perspectives in macromolecular design for both nanoscience and biomedicine.

Synthesis of Peptide-Functionalized Poly(bis-sulfone) Copolymers Regulating HIV-1 Entry and Cancer Stem Cell Migration.

Peptide-polymer conjugates have been regarded as primary stronghold in biohybrid nanomedicine, which has seen extensive development due to its intrinsic property to provide complementary functions of both the peptide material and the synthetic polymer platform. Here we present an advanced macromolecular therapeutic that targets two exclusive classes of important diseases (namely, the HIV and cancer) that are implicated by extremely different causative agents. Using a facile thiol-reactive monomer, the eventual polymer facilitates multivalent conjugation of an endogenous peptide WSC02 that targets the CXCR4 chemokine receptor. The biohybrid material demonstrated both potent antiviral effects against HIV-1 as well as inhibiting cancer stem cell migration thus establishing the foundation for multimodal nanotherapeutics that simultaneously target more than one class of disease implications.

Biocompatible micelles based on comb-like PEG derivates: formation, characterization, and photo-responsiveness.

A novel comb-like derivative CPEG-g-DNQ was prepared by incorporating light responsive 2-diazo-1,2-naphthoquinone (DNQ) groups into the structure of comb-like poly(ethylene glycol) (CPEG). DLS and TEM results showed that CPEG-g-DNQ self-assembled into spherical micelles with an average size of about 135 nm in water. Upon exposure to light, the micelles could be disrupted because of the conversion of hydrophobic DNQ to hydrophilic 3-indenecarboylic acid. Additionally, hydrophobic coumarin 102 was successfully loaded into the micelles and photo-induced ON-OFF release was demonstrated by fluorescence spectroscopy. MTT assay revealed that the micelles are biocompatible. These photo-responsive micelles might have great potential for controlled release of hydrophobic drugs.