High Entropy 2D Layered Double Hydroxide Nanosheet Toward Cascaded Nanozyme-Initiated Chemodynamic and Immune Synergistic Therapy.

High-entropy nanomaterials (HEMs) are a hot topic in the fields of energy and catalysis. However, in terms of promising biomedical applications, potential therapeutic studies involving HEMs are unprecedented. Herein, we demonstrated high entropy two-dimensional layered double hydroxide () nanoplatforms with versatile physicochemical advantages that reprogram the tumor microenvironment (TME) and provide antitumor treatment via cascaded nanoenzyme-initiated chemodynamic and immune synergistic therapy.

Construction of CXCR4 Receptor-Targeted CuFeSe Nano Theranostic Platform and Its Application in MR/CT Dual Model Imaging and Photothermal Therapy.

Introduction: Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need.

Methods: We introduce an "all-in-one" tumor-targeted theranostic platform using CuFeSe-based composite nanoparticles (CuFeSe@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation.

A COX2-targeting cancer-specific fluorescent probe for hydrogen sulfide detection in living cells, , and zebrafish.

A novel cyclooxygenase-2 (COX-2) targeted HS-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This HS-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, (), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous HS in living cells, demonstrating high sensitivity and specificity and strong anti-interference.

Manganese-functionalized MXene theranostic nanoplatform for MRI-guided synergetic photothermal/chemodynamic therapy of cancer.

Two-dimensional transition metal carbides and nitrides (MXenes) nanosheets with high photothermal conversion efficiency as well as photothermal stability can efficiently generate remarkable hyperthermia for photothermal therapy (PTT) of cancer. However, mono-MXenes cannot exhibit precise diagnosis and treatment to complete ablation of cancer cells in the PTT process. To overcome this dilemma, an "all-in-one" nanoplatform of titanium carbide (TiC) MXene-based composite nanosheets is developed for magnetic resonance imaging (MRI)-guided multi-modal hyperthermia and chemodynamic tumor ablation, which was achieved by bonding of manganese ion on the surface of TiC, and then was the functionalized nanosheets was modified by biocompatible PEG (Mn-TiC@PEG).

A covalent organic framework with a self-contained light source for photodynamic therapy.

External light-independent antitumor PDT is successfully realized with a covalent organic framework (COF)-based host-guest nanosystem. Its highly effective antitumor behavior is fully demonstrated by both HO-overexpressed 4T1 and HO-less expressed HCT116 and MCF-7 xenograft models.

Multimodal molecular imaging evaluation for early diagnosis and prognosis of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive and lethal malignancy with limited therapeutic options. Despite recent advances in diagnostic imaging for CCA, the early diagnosis of CCA and evaluation of tumor invasion into the bile duct and its surrounding tissues remain challenging. Most patients with CCA are diagnosed at an advanced stage, at which treatment options are limited.

Fluorescence imaging of pathophysiological microenvironments.

Abnormal microenvironments (viscosity, polarity, pH, etc.) have been verified to be closely associated with numerous pathophysiological processes such as inflammation, neurodegenerative diseases, and cancer. As a result, deep insights into these pathophysiological microenvironments are particularly beneficial for clinical diagnosis and treatment.

A covalent organic framework-based nanoagent for HS-activable phototherapy against colon cancer.

Herin, we report a Cu(ii)-porphyrin-derived nanoscale COF, which can be triggered by endogenous HS via an intracellular sulfidation reaction to generate a metal-free COF-photosensitizer for PDT against HS-enriched colon tumors with controllable singlet oxygen release; meanwhile in situ generated CuS can be synchronously used as a photothermal agent for PTT.

Core-Shell-Structured Covalent-Organic Framework as a Nanoagent for Single-Laser-Induced Phototherapy.

Imaging-guided phototherapy, including photothermal therapy and photodynamic therapy, has been emerging as a promising avenue for precision cancer treatment. However, the utilization of a single laser to induce combination phototherapy and multiple-model imaging remains a great challenge. Herein, we report, the first of its kind, a covalent-organic framework (COF)-based magnetic core-shell nanocomposite, , that is used as a multifunctional nanoagent for cancer theranostics under single 660 nm NIR irradiation.

Polydopamine-Based Multifunctional Antitumor Nanoagent for Phototherapy and Photodiagnosis by Regulating Redox Balance.

The development of multifunctional nanoagents for the simultaneous achievement of high diagnostic and therapeutic performances is significant for precise cancer treatment. Herein, we report on a polydopamine (PDA)-based multifunctional nanoagent, , in which the methylene blue (MB) photosensitizer (PS) and l-arginine (l-Arg) tumor-targeting species are equipped. After selectively accumulating in tumor sites, glutathione (GSH)-responsive degradation can controllably release loaded MB to produce singlet oxygen (O) under near-infrared (NIR) photoirradiation.

Design and applications of a novel fluorescent probe for detecting glutathione in biological samples.

This study aimed to develop a novel and practical fluorescent method for GSH detection in complex biological samples. To this end, a series of coumarin-based fluorescent probes was designed and synthesized using various aliphatic halogens as the sensing group. By using a new evaluation method of GSH/Cys/Hcy coexisting conditions, the probe with chloropropionate (CBF3) showed a high selectivity, excellent sensitivity, good stability for GSH detection.

Binary Drug Reinforced First Small-Molecule-Based Prodrug for Synergistic Anticancer Effects.

We developed a small-molecule-based binary drug delivery system (BDDS) with two anticancer drugs, SN-38 and 5'-DFUR. The drug release from the prodrug BDDS can be achieved upon its reaction with intracellular HO, overexpressed in cancer cells. The efficacy of BDDS was demonstrated by a comparative study along with that of a single drug conjugate (SDDS), bearing SN-38 alone.

A mitochondria-targeted two-photon fluorescent probe for sensing and imaging pH changes in living cells.

A novel two-photon pH probe, 3-benzimidazole-7-hydroxycoumarin (BHC), was designed and synthesized based on the structures of hydroxycoumarin and benzimidazole. BHC showed good linearity in the pH ranges of 3.30-5.

Environmental Benzopyrene Attenuates Stemness of Placenta-Derived Mesenchymal Stem Cells via Aryl Hydrocarbon Receptor.

The toxic effects of particulate matter have been linked to polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene. PAHs are potent inducers of the aryl hydrocarbon receptor (AhR), which is an expressed nuclear receptor that senses environmental stimuli and modulates gene expression. Even though several studies have shown that the benzopyrene (BP) of chemical pollutants significantly impaired stem cell activity, the exact molecular mechanisms were not clearly elucidated.

A ratiometric fluorescent probe for detecting hypochlorite in the endoplasmic reticulum.

A colorimetric and fluorescent probe ER-ClO was presented in this work to detect cellular hypochlorite with high selectivity and sensitivity. With an organelle targeting unit, ER-ClO was successfully applied in the bio-imaging of exogenous and endogenous hypochlorite in the endoplasmic reticulum in a ratiometric manner.

COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer therapy in preclinical models.

Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as an important component in current cancer therapeutic modalities.

Omnipotent phosphorene: a next-generation, two-dimensional nanoplatform for multidisciplinary biomedical applications.

Phosphorene, also known as single- or few-layer black phosphorus (FLBP), is a new member of the two-dimensional (2D) material family and has attracted significant attention in recent years for applications in optoelectronics, energy storage and biomedicine due to its unique physicochemical properties and excellent biocompatibility. FLBP is regarded as a potential biological imaging agent for cancer diagnosis due to its intrinsic fluorescence (FL) and photoacoustic (PA) properties and negligible cytotoxicity. FLBP-based photothermal and photodynamic therapies have emerged with excellent anti-tumour therapeutic efficacies due to their unique physical properties, such as near-infrared (NIR) optical absorbance, large extinction coefficients, biodegradability and reactive oxygen species (ROS) or heat generation upon light irradiation.

PLK1-Targeted Fluorescent Tumor Imaging with High Signal-to-Background Ratio.

As significantly expressed during cell division, polo-like kinase 1 (PLK1) plays crucial roles in numerous mitotic events and has attracted interest as a potential therapeutic marker in oncological drug discovery. We prepared two small molecular fluorescent probes, 1 and 2, conjugated to SBE13 (a type II PLK1 inhibitor) to investigate the PLK1-targeted imaging of cancer cells and tumors. Enzymatic docking studies, molecular dynamics simulations, and in vitro and in vivo imaging experiments all supported the selective targeting and visualization of PLK1 expressing cells by probes 1 and 2, and probe 2 was successfully demonstrated to image PLK1-upregulated tumors with remarkable signal-to-background ratios.

Fluorescent bioimaging of pH: from design to applications.

Protons play crucial roles in many physiological and pathological processes, such as receptor-mediated signal transduction, ion transport, endocytosis, homeostasis, cell proliferation, and apoptosis. The urgent demand for pH imaging and measurement in biological systems has incited the development of fluorescent pH probes. Numerous fluorescent probes have been reported, but many lack the abilities needed for biological applications.

Highly selective two-photon imaging of cysteine in cancerous cells and tissues.

Abnormal concentrations of Cys have been reported to be implicated in various health problems, including cancer, neuropathy, and cardiomyopathy. We present a novel two-photon fluorescent probe for the specific recognition of cysteine over homocysteine and glutathione, and the bioapplication of this probe for the imaging of live cancerous cells and thick tissues.

Recent development of biotin conjugation in biological imaging, sensing, and target delivery.

Despite encouraging results from preliminary studies of anticancer therapies, the lack of tumor specificity remains an important issue in the modern pharmaceutical industry. New findings indicate that biotin or biotin-conjugates could be favorably assimilated by tumor cells that over-express biotin-selective transporters. Furthermore, biotin can form stable complexes with avidin and its bacterial counterpart streptavidin.

Mitochondrial induced and self-monitored intrinsic apoptosis by antitumor theranostic prodrug: in vivo imaging and precise cancer treatment.

Activation of apoptosis, the cell death machinery, in tumor cells by organelle-specific delivery of antitumor theranostic agent is the utmost challenge in cancer therapy. Herein, we developed a highly efficient mitochondria-targeting antitumor theranostic prodrug 7 that contained two molecules of drug 5'-deoxy-5-fluorouridine and an apoptotic marker ethidium for self-monitoring intrinsic (mitochondrial) apoptosis after its activation in tumor cells. Theranostic 7 was activated by endogenously produced mitochondrial-overexpressed H2O2 and released drug 5'-deoxy-5-fluorouridine and apoptotic marker ethidium to the tumor cells.

A Nile Red/BODIPY-based bimodal probe sensitive to changes in the micropolarity and microviscosity of the endoplasmic reticulum.

We herein report a fluorescent bimodal probe (1) capable of determining ER viscosity and polarity changes using FLIM and fluorescence ratiometry, respectively; during ER stress caused by tunicamycin, the viscosity was increased from ca. 129.5 to 182.

A fluorescent probe to detect thiol-containing amino acids in solid tumors.

Early detecting of cancer is critical to provide proper treatment and to improve survival of patients. Here, we reported a highly sensitive ratiometric (yellow emission (550 nm) to blue emission (496 nm)) fluorescent probe 1 developed for detection of thiol-containing amino acids. This probe successfully eliminates interference from background autofluorescence, and discriminates between human carcinoma and normal cells by detecting intracellular thiol levels in living cells (P < 0.

Fluorescent and colorimetric sensors for detection of lead, cadmium, and mercury ions.

Exposure to even very low levels of lead, cadmium, and mercury ions is known to cause neurological, reproductive, cardiovascular, and developmental disorders, which are more serious problems for children particularly. Accordingly, great efforts have been devoted to the development of fluorescent and colorimetric sensors, which can selectively detect lead, cadmium, and mercury ions. In this critical review, the fluorescent and colorimetric sensors are classified according to their receptors into several categories, including small molecule based sensors, calixarene based chemosensors, BODIPY based chemosensors, polymer based chemosensors, DNA functionalized sensing systems, protein based sensing systems and nanoparticle based sensing systems (197 references).