Such porous materials not only effectively avoid unwanted active site accumulation induced quenching (ACQ) and offer sufficient contact with guest molecules to favor their exchange and diffusion, but more importantly, finely tune their band energy and optical properties via formation of covalently linked crystalline domains. [2] In this study, this strategy was utilized to form a series of multienzyme-mimicking covalent organic frameworks by decorating metal ions (Cu, Fe and Ni) into the COF backbone, where their optical properties, including band energy, lifetime, and lightabsorption properties, were finely tuned to achieve excellent enzyme-mimicking catalytic performance, including superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx) activities. As a result, one member, COF-909-Cu was revealed to be a good pyroptosis inducer for boosting cancer immunotherapy for the first time.As a form of noninflammatory programmed cell death (PCD), the efficacy of apoptosis is usually limited due to the existence of apoptosis resistance in cancer cells, leading to unsatisfactory therapeutic performance. [3] In contrast to apoptosis, pyroptosis and ferroptosis are immunogenic PCD and are recently proven to be a powerful strategy to combat cancer, owing to their favorable ability to prime antitumor immune responses by releasing sufficient danger-associated molecular patterns (DAMPs). [4] Attempts have been made to isolate iron ions into the building block of MOF to facilitate the pyroptosiseliciting process and activate the immune system. [5] Recently, COFs were also utilized as new photosensitizers (PSs) for chemodynamic therapy (CDT)-triggered ferroptosis. [6] The potential of inducing pyroptosis by using COF materials, however, is rarely explored due to the stringent requirement for an acute inflammatory response. Moreover, the hypoxic character in the tumor microenvironment (TME) and limited penetration depth also restrict the reactive oxygen species (ROS) generation efficiency of photodynamic therapy (PDT). [7] CDT, which involves the consumption of intracellular hydrogen peroxide (H 2 O 2 ) to produce hydroxyl radicals (•OH), the most harmful ROS, is promising for eliciting acute inflammatory responses and inducing pyroptosis due to the advantages of not relying The engineering of a series of multienzyme-mimicking covalent organic frameworks (COFs), COF-909-Cu, COF-909-Fe, and COF-909-Ni, as pyroptosis inducers, remodeling the tumor microenvironment to boost cancer immunotherapy, is reported. Mechanistic studies reveal that these COFs can serve as hydrogen peroxide (H 2 O 2 ) homeostasis disruptors to elevate intracellular H 2 O 2 levels, and they not only exhibit excellent superoxide dismutase (SOD)-mimicking activity and convert superoxide radicals (O 2 •− ) to H 2 O 2 to facilitate H 2 O 2 generation, but also possess outstanding glutathione peroxidase (GPx)-mimicking activity and deplete glutathione (GSH) to alleviate the scavenging of H 2 O 2 . Meanwhile, the outstanding photothermal the...
Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared – non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.
The synergistic efficacy of phototherapy and cancer immunotherapy is severely restricted by both the inherent photobleaching and aggregation‐caused quench (ACQ) defects of photosensitizers and the intrinsic antioxidant tumor microenvironment (TME), such as hypoxia and overexpressed glutathione (GSH). To address these issues, a novel porphyrin‐based staggered stacking covalent organic framework (COF), COF‐618‐Cu, is rationally designed as a reactive oxygen species (ROS) amplifier, owing to its excellent catalase‐like activity, COF‐618‐Cu is capable of consuming endogenous hydrogen peroxide to produce sufficient oxygen to alleviate the tumor hypoxia phenomena. Moreover the overexpressed intracellular GSH is also depleted to decrease the scavenging of ROS, due to the glutathione peroxidase mimic activity of COF‐618‐Cu. Mechanistic studies reveal that the unique staggered stacking mode between COF‐618‐Cu interlayers can effectively relieve both the photobleaching and ACQ effects that are inaccessible to commonly eclipsed COFs. These, combined with their excellent photothermal therapy performance, make COF‐618‐Cu favorable for inducing robust immunogenic cell death and remodeling TME to boost antitumor immunity.
Nondegradable heavy metals have caused great dangers to the environment and human health. Combining stimuli-responsive materials with conventional MOF-based adsorbents has been considered an effective method to generate intelligent adsorbents for superior control over the adsorption process. Herein, a smart MOF-based ratiometric fluorescent adsorbent was designed to accurately monitor the progression of the removal of copper ions with dual-emitting fluorescence signal. Unlike the traditional difunctional materials, this delicately designed platform overcomes the huge energy gap to achieve two functions simultaneously. This unconventional platform provides a reliable fluorescent response toward Cu2+ during the removing process, changing linearly related to the degree of the adsorption process, which holds extreme promise in effectively monitoring the adsorption process. The underlying relationship of the adsorption and fluorescence response process toward copper was investigated by density functional theory (DFT) calculations. In particular, because of the favorable ion binding affinity of ZIF-8 and self-calibrating effect of RhB, the as-prepared smart adsorbent demonstrates a superior adsorption performance of 608 mg g–1, broad response range (0.05–200 ppm, 2.07 × 10–7to 8.29 × 10–4 M), ultrahigh sensitivity (0.04 ppm, 1.91 × 10–7 M) toward Cu2+ and strong anti-interference ability. This smart adsorbent opens an intelligent pathway to promote substantial advancements in the fields of environmental monitoring and industrial waste management.
Covalent organic frameworks (COFs) with 2D pconjugation were designed and synthesized as molecular photosensitizers for efficient photodynamic therapy.
In this study, we constructed a novel solid state supramolecular system-the molecular cage ZnOTCPP, based on an inorganic/organic hybrid nanostructure, through the assembly of 5,10,15,20-tetra(3-carboxyphenyl)porphyrin (TCPP) onto the surfaces of ZnO nanorod (NR) arrays. The ZnOTCPP molecular cage exhibited highly selective recognition of 5,10,15,20-tetraphenylporphyrin (TPP) by optical and photoelectrical signals. The ZnOTCPP@TPP exhibited high emission efficiency, with a six-fold increase in the intensity of the emission relative to that of ZnOTCPP after the molecular cage ZnOTCPP captured TPP. The optical, electrical, and optoelectrical properties of the molecular cage ZnOTCPP could be controlled by tuning the interactions between the guest and the host's inorganic or organic moieties. Such a solid state molecular cage opens the door to controlled-delivery applications and provides an attractive platform for studying solid state supramolecular electronics and optoelectronics.
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