Shedding light on cellular dynamics: the progress in developing photoactivated fluorophores.

Photoactivated fluorophores (PAFs) are highly effective imaging tools that exhibit a removal of caging groups upon light excitation, resulting in the restoration of their bright fluorescence. This unique property allows for precise control over the spatiotemporal aspects of small molecule substances, making them indispensable for studying protein labeling and small molecule signaling within live cells. In this comprehensive review, we explore the historical background of this field and emphasize recent advancements based on various reaction mechanisms.

NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma.

Background: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear.

An ortho-activation strategy to develop NIR fluorescent probe for rapid imaging of biothiols in vivo.

Biothiols are the main antioxidants in regulating the redox balance and resisting oxidative stress in various biological processes, but the long detection time of current fluorescent probes hinders their rapid imaging in vitro and in vivo. To reveal the influx of biothiols, we rationally develop an ortho-activation approach to accelerate the reaction between the probe and biothiols, by introducing electron-withdrawing fluorine atom into the ortho-site of the phenolic hydroxyl group in the NIR probe to generate an ortho-inductive effect. The ortho-fluorine helps to increase the chemical reactivity of the molecular structure, resulting in a significantly shorter detection time (within 5 min) as compared to previous reports (> 20 min for acrylates-based probes in aqueous solution).

Air pollution particles hijack peroxidasin to disrupt immunosurveillance and promote lung cancer.

Although fine particulate matter (FPM) in air pollutants and tobacco smoke is recognized as a strong carcinogen and global threat to public health, its biological mechanism for inducing lung cancer remains unclear. Here, by investigating FPM's bioactivities in lung carcinoma mice models, we discover that these particles promote lung tumor progression by inducing aberrant thickening of tissue matrix and hampering migration of antitumor immunocytes. Upon inhalation into lung tissue, these FPM particles abundantly adsorb peroxidasin (PXDN) - an enzyme mediating type IV collagen (Col IV) crosslinking - onto their surface.

A phase-transfer catalyst-based nanoreactor for accelerated hydrogen sulfide bio-imaging.

Hydrogen sulfide (HS) is an important signaling molecule in various biological processes; however, its real-time monitoring in living cells is hampered by long detection time for current fluorescent probes. To overcome this challenge, we designed a phase-transfer catalyst (PTC) approach to accelerate the reaction between the probe and the analyte by conjugating common fluorescent probes - mostly hydrophobic small molecules - with an amphiphilic PEG-PPG-PEG polymer, enabling the controllable assembly of HS nanoprobes in an aqueous solution. The PEG block helps to establish a PTC microenvironment that endows the assembled nanoprobes with a significantly reduced detection time (3-10 min; 20-60 min for small-molecule probes).

An "all-in-one" scaffold targeting macrophages to direct endogenous bone repair in situ.

Scaffolds for tissue repair are designed in an increasingly complicated manner to meet multi-facet biological needs during the healing process. However, overly sophisticated design, especially the use of multiple components and delivery of exogenous cells, hampers the bench-to-bedside translation. Here, a multi-functional - yet mono-compositional - bioactive scaffold is devised to mediate the full-range, endogenous bone repair.

A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo.

Near-infrared (NIR) fluorescent probes are among the most attractive chemical tools for biomedical imaging. However, their in vivo applications are hindered by albumin binding, generating unspecific fluorescence that masks the specific signal from the analyte. Here, combining experimental and docking methods, we elucidate that the reason for this problem is an acceptor (A) group-mediated capture of the dyes into hydrophobic pockets of albumin.

Engineering a microcarrier based on a polysaccharide-growth factor complex for enhancing the proliferation of mesenchymal stem cells.

Mesenchymal stem cell (MSC) delivery has been broadly investigated as a cell-based therapy strategy towards various diseases and tissue injury. In these applications, the cell-delivery vehicle plays a crucial role in determining the therapeutic performance of MSCs and their fate post-implantation. We report here the development of a microcarrier system combining platelet-derived growth factor-BB (PDGF-BB) and a PDGF-BB-binding polysaccharide - Eucommia ulmoides (EUP3) - for MSC cultivation.

A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages.

Switching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design.

Water solubility is essential for fluorescent probes to image hypochlorous acid in live cells.

We synthesised four probes and compared their HClO-detecting ability in different solvents. The data showed that only hydrophilic probes could sensitively and accurately detect HClO in live cells. Meanwhile, the addition of organic solvents, as is commonly practised, weakens the oxidising capacity of HClO and thus generates inaccurate outcomes.

A Water-Soluble, Two-Photon Probe for Imaging Endogenous Hypochlorous Acid in Live Tissue.

Detection of hypochlorous acid (HClO) in the living system may help to uncover its essential biological functions. However, current imaging agents suffer from poor water solubility that limit their live-tissue applications. Here, a water-soluble probe (NNH) is devised through innovative hydrazone modification of 1,8-naphthalimide at 3' position.

Bioactive polysaccharides from natural resources including Chinese medicinal herbs on tissue repair.

Background: Functional polysaccharides can be derived from plants (including herbs), animals and microorganisms. They have been widely used in a broad of biomedical applications, such as immunoregulatory agents or drug delivery vehicles. In the past few years, increasing studies have started to develop natural polysaccharides-based biomaterials for various applications in tissue engineering and regenerative medicine.

An ortho-aldehyde modified probe to image thiols in living cells with enhanced selectivity.

Developing fluorescent probes to image thiols in the living system may provide powerful tools to study the functions of thiol-containing biological molecules. In this study, we report the design and evaluation of a novel turn-on fluorescent probe NQNO for selective detection of thiols in living cells. By introducing an ortho-aldehyde group to NNO, a conventional compound representing a class of thiol-imaging strategy, we obtained NQNO with enhanced selectivity for thiols over the major interferent hydrogen sulfide (HS).

Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: Design of a glucomannan coating material.

The biomaterials-host interaction is a dynamic process in which macrophages play a vital role of regulation. Depending on the biochemical signals they sense, these highly plastic cells can mediate the immune response against the implanted scaffolds and/or exert regenerative potency to varying extent. Designing appropriate 'exterior signals' for scaffolds may exploit the power of endogenous macrophages to aid the regeneration of engineered tissues.

A dinuclear ruthenium(II) complex as turn-on luminescent probe for hypochlorous acid and its application for in vivo imaging.

A dinuclear ruthenium(II) complex Ruazo was designed and synthesized, in which oxidative cyclization of the azo and o-amino group was employed for the detection of hypochlorous acid (HClO) in aqueous solution. The non-emissive Ruazo formed highly luminescent triazole-ruthenium(II) complex in presence of HClO and successfully imaged HClO in living cell and living mouse.

HEPES is not suitable for fluorescence detection of HClO: a novel probe for HClO in absolute PBS.

HEPES is not suitable for fluorescence detection of HClO because it can be oxidized by HClO. A novel probe for HClO, which can selectively and sensitively detect HClO in absolute PBS, was developed on the basis of an oxidation reaction with an azo moiety. Furthermore, it works well in live mouse imaging.

Ratiometric and colorimetric near-infrared sensors for multi-channel detection of cyanide ion and their application to measure β-glucosidase.

A near-infrared sensor for cyanide ion (CN(-)) was developed via internal charge transfer (ICT). This sensor can selectively detect CN(-) either through dual-ratiometric fluorescence (logarithm of I414/I564 and I803/I564) or under various absorption (356 and 440 nm) and emission (414, 564 and 803 nm) channels. Especially, the proposed method can be employed to measure β-glucosidase by detecting CN(-) traces in commercial amygdalin samples.