Tumor and intratumoral pathogen cascade-targeting photothermal nanotherapeutics for boosted immunotherapy of colorectal cancer.

Clinical benefits of immunotherapy in colorectal cancer (CRC) are limited due to the low immunogenicity and immunosuppressive tumor microenvironment. Fusobacterium nucleatum (Fn) is discovered to colonize CRC tumors and dampen immunotherapy by fostering an immunosuppressive TME. Herein, a controllable "Shielding-deshielding" N-acetylgalactosamine (GalNAc)-derived photothermal nanotherapeutic is developed to mediate cascade targeting toward tumor and intratumoral Fn for enhanced photothermal-immunotherapy.

Remodeling the Inflammatory and Immunosuppressive Tumor Microenvironment for Enhancing Antiangiogenic Gene Therapy of Colorectal Cancer.

Fusobacterium nucleatum (Fn), as an intestinal pathogenic bacterium, is closely related to the occurrence, progression, and limited therapeutic efficacy of colorectal cancer (CRC). The presence of Fn within CRC communities induces an inflammatory and immunosuppressive microenvironment while promoting new vessel formation. Therefore, developing novel methods to efficiently eliminate Fn and enhance the therapeutic outcomes against Fn-associated CRC is of great significance.

Engineering lauric acid-based nanodrug delivery systems for restoring chemosensitivity and improving biocompatibility of 5-FU and OxPt against -associated colorectal tumor.

Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided () could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for -associated CRC treatment.

PAFAH2 suppresses synchronized ferroptosis to ameliorate acute kidney injury.

Synchronized ferroptosis contributes to nephron loss in acute kidney injury (AKI). However, the propagation signals and the underlying mechanisms of the synchronized ferroptosis for renal tubular injury remain unresolved. Here we report that platelet-activating factor (PAF) and PAF-like phospholipids (PAF-LPLs) mediated synchronized ferroptosis and contributed to AKI.

In situ-activated photothermal nanoplatform for on-demand NO gas delivery and enhanced colorectal cancer treatment.

The naturally evolved and intestinal pathogenic Fusobacterium nucleatum (Fn)-induced drug resistance profoundly impaired the efficacy of chemotherapy against colorectal cancer (CRC). Alternative treatment modalities against Fn-associated CRC are desperately needed. Herein, we engineer an in situ-activated anti-tumor and antibacterial nanoplatform (CuO/BNN6@MSN-Dex) to allow photoacoustic (PA) imaging-guided photothermal and NO gas combinatorial therapy for enhanced Fn-associated CRC treatment.

A Photosensitive Polymeric Carrier with a Renewable Singlet Oxygen Reservoir Regulated by Two NIR Beams for Enhanced Antitumor Phototherapy.

Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen ( O ) upon laser irradiation to ablate tumors, will exacerbate the already oxygen shortage of most solid tumors and is thus self-limiting. Herein, a sophisticated photosensitive polymeric material (An-NP) that allows sustained O generation and sufficient oxygen supply during the entire phototherapy is engineered by alternatively applying PDT and photothermal therapy (PTT) controlled by two NIR laser beams. In addition to a photosensitizer that generates O , An-NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing O with superior reversibility and a dye J-aggregate with superb photothermal performance.

A Supramolecular Strategy to Engineering a Non-photobleaching and Near-Infrared Absorbing Nano-J-Aggregate for Efficient Photothermal Therapy.

The design of organic photothermal agents (PTAs) for applications face a demanding set of performance requirements, especially intense NIR-absorptivity and sufficient photobleaching resistance. J-aggregation offers a facile way to tune the optical properties of dyes, thus providing a general design platform for organic PTAs with the desired performance. Herein, we present a supramolecular strategy to build a water-stable, nonphotobleaching, and NIR-absorbing nano-PTA (J-NP) from J-aggregation of halogenated BODIPY dyes (BDP) for efficient photothermal therapy.

Rational molecular design of a reversible BODIPY-Based fluorescent probe for real-time imaging of GSH dynamics in living cells.

Marring the reversible covalent chemistry with BODIPY dye, which is a superfamily of fluorophores with striking photophysical performances, would enable a panel of diverse dynamic fluorescent probes for biomedical applications. Herein we show that structural manipulation of BODIPY allows rational tuning of α-site or meso-site activation as well as the spectral response toward nucleophiles. By rational molecular design, we have obtained a highly specific and reversible GSH probe, BD-GSH, which exhibits a tremendously fast and dynamic fluorescence response within the wide physiological GSH concentration range of 0-8 mM.

Central rather than brachial pressures are stronger predictors of cardiovascular outcomes: A longitudinal prospective study in a Chinese population.

The purpose of this study was to assess the association of blood pressure (BP) measurements with the risk of cardiovascular disease (CVD) and examine whether central systolic BP (CSBP) predicts CVD better than brachial BP measurements (SBP and pulse pressure [PP]). Based on a cross-sectional study conducted in 2009-2010 with follow-up in 2016-2017 among 35- to 64-year-old subjects in China, we evaluated the performance of non-invasively predicted CSBP over brachial BP measurements on the first CVD events. Each BP measurement, individually and jointly with another BP measurement, was entered into the multivariate Cox proportional-hazards models, to examine the predictability of central and brachial BP measurements.

Two Orthogonal Halogen-Bonding Interactions Directed 2D Crystalline Supramolecular J-Dimer Lamellae.

Dye assemblies exhibit fascinating properties and performances, both of which depend critically on the mutual packing arrangement of dyes and on the supramolecular architecture. Herein, we engineered, for the first time, an intriguing chlorosome-mimetic 2D crystalline J-dimer lamellar structure based on halogenated dyes in aqueous media by employing two distinct orthogonal halogen-bonding (XB) interactions. As the only building motif, antiparallel J-dimer was formed and stabilized by single π-stacking and dual halogen⋅⋅⋅π interactions.

Nano-Assemblies from J-Aggregated Dyes: A Stimuli-Responsive Tool Applicable To Living Systems.

Controlling the packing arrangements of dyes is a facile way of tuning their photophysical and/or photochemical properties, thus enabling new sensing mechanisms for photofunctional tools. Here, we present a general and robust strategy toward water-stable J-aggregated dye-templated nanoassemblies by incorporating an amphiphilic diblock copolymer and a stimuli-responsive dye as the only two building components. An iodo-substituted boron dipyrromethene (BODIPY) was adopted as a template to direct the self-assembly of poly(ethylene glycol)- block-polycaprolactone (PEG-PCL), forming a core-shell nanoplate with slip-stacked BODIPYs as core surrounded by hydrophilic PEG shell.

A General Strategy Toward Highly Fluorogenic Bioprobes Emitting across the Visible Spectrum.

A general approach toward highly fluorogenic probes across the visible spectrum for various analytes offers significant potential for engineering a wide range of bioprobes with diverse sensing and imaging functions. Here we show a facile and general strategy that involves introducing a new fluorogenic mechanism in boron dipyrromethene (BODIPY) dyes, based on the principle of stimuli-triggered dramatic reduction in the electron-withdrawing capabilities of the meso-substituents of BODIPYs. The fluorogenic mechanism has been demonstrated to be applicable in various BODIPYs with emission maxima ranging from green to far red (509, 585, and 660 nm), and the synthetic strategy allows access to a panel of highly fluorogenic bioprobes for various biomolecules and enzymes (HO, HS, and protease) via introducing specific triggering motifs.