Fluorescent dyes with multi-functionality are of great interest for photo-based cancer theranostics. However, their low singlet oxygen quantum yield impedes their potential applications for photodynamic therapy (PDT). Now, a molecular self-assembly strategy is presented for a nanodrug with a remarkably enhanced photodynamic effect based on a dye-chemodrug conjugate. The self-assembled nanodrug possesses an increased intersystem crossing rate owing to the aggregation of dye, leading to a distinct singlet oxygen quantum yield (Φ( O )). Subsequently, upon red light irradiation, the generated singlet oxygen reduces the size of the nanodrug from 90 to 10 nm, which facilitates deep tumor penetration of the nanodrug and release of chemodrug. The nanodrug achieved in situ tumor imaging and potent tumor inhibition by deep chemo-PDT. Our work verifies a facile and effective self-assembly strategy to construct nanodrugs with enhanced performance for cancer theranostics.
Studies on the azobenzene derivative based phase transitions mostly rely on photoisomerization, which require a long time to spontaneously revert back. Here we show a photothermal-driven solid-to-liquid transition and fast reversion of azobenzene derivatives. Owing to the aggregation of suitably substituted azobenzenes, solid-to-liquid transitions can be induced by photothermal effects under irradiation with green light. The liquid-state azobenzene derivatives spontaneously solidify again within 2 min due to heat release in a purely physical fashion. One thus obtains a perfectly reversible adhesion with a strength as high as that of commercial materials. Our work affords a novel concept to construct reversible adhesives via phase transitions of organic compounds induced by light.
CONSPECTUS: Fighting cancer with the means of chemistry remains a tremendous challenge and defines a pressing societal need. Compounds based on synthetic organic dyes have long been recognized as vital tools for cancer diagnosis and therapy (theranostics). Fluorescence and photoacoustic imaging of cancer as well as cancer treatment protocols such as photodynamic and photothermal therapy are all photobased technologies that require chromophores. However, a serious drawback of most chromophoric molecules is photobleaching over the course of their use in biological environments, which severely compromises the desired theranostic effects. At this point, rylenecarboximide (RI) dyes with ultrahigh photostability hold enormous promise. RI stands for a homologous series of dyes consisting of an aromatic core and carboximide auxochromic groups. They possess high molar extinction coefficients and finely tunable photophysical properties. RIs such as perylenebiscarboxylic acid monoimide (PMI), perylenetetracarboxylic acid diimide (PDI), terrylenetetracarboxylic acid diimide (TDI), and quaterrylene tetracarboxylic acid diimide (QDI) have attracted great scientific attention as colorants, components of organic photovoltaics and organic field-effect transistors, as well as tools for biological applications. PDI has appeared as one of the most widely studied RI dyes for fluorescence bioimaging. Our recent breakthroughs including chemotherapy with PDI-based DNA intercalators and photothermal therapy guided by photoacoustic imaging using PDI, TDI, or QDI, define urgent needs for further scientific research and clinical translation. In this Account, we tackle the relationship between chemical structures and photophysical and pharmacologic properties of RIs aiming at new contrast and anticancer agents, which then lay the ground for further biomedical applications. First, we introduce the design concepts for RIs with a focus on their structure−property relationships. Chemical structure has an enormous impact on the fluorescent, chemotoxic, photodynamic, and photothermal performance of RIs. Next, based on the resulting performance criteria, we employ RIs for fluorescence and photoacoustic cancer imaging as well as cancer therapies. When carrying electron donating substituents, PDIs and PMIs possess high fluorescence quantum yield and red-shifted emission which qualifies them for use in cancer fluorescence imaging. Also, some fluorescent PDIs are combined with chemodrugs or developed into DNA intercalators for chemotherapy. PDI-based photosensitizers are prepared by "heavy atom" substitution, showing potential for photodynamic therapy. Further, photothermal agents using PDI, TDI, and QDI with near-infrared absorption and excellent photothermal conversion efficiency offer high promise in photothermal cancer therapy monitored by photoacoustic imaging. Finally, looking jointly at the outstanding properties of RIs and the demands of current biomedicine, we offer an outlook toward further modifications of RIs as a powerful and practical pla...
Two-dimensional (2D) nanosheets (NSs) have a large surface area, high surface free energy, and ultrathin structure, which enable them to more easily penetrate biological membranes and promote adsorption of drugs and proteins. NSs are capable of adsorbing a large amount of blood proteins to form NSs–protein corona complexes; however, their inflammatory effects are still unknown. Therefore, we investigated the pro-inflammatory effect of 2D model nanosheet structures, molybdenum disulfide (MoS2), and the MoS2 NSs–protein complexes with four abundant proteins in human blood, i.e., human serum albumin (HSA), transferrin (Tf), fibrinogen (Fg), and immunoglobulin G (IgG). The interactions between the NSs and the proteins were analyzed by quantifying protein adsorption, determining binding affinity, and correlating structural changes in the protein corona with the uptake of NSs by macrophages and the subsequent inflammatory response. Although all of the NSs–protein complexes induced inflammation, IgG-coated and Fg-coated NSs triggered much stronger inflammatory effects by producing and releasing more cytokines. Among the four proteins, IgG possessed the highest proportion of β-sheets and led to fewer secondary structure changes on the MoS2 nanosheets. This can facilitate uptake and produce a stronger pro-inflammatory response in macrophages due to the recognition of an NSs–IgG complex by Fc gamma receptors and the subsequent activation of the NF-κB pathways. Our results demonstrate that the blood protein components contribute to the inflammatory effects of nanosheets and provide important insights for the nanosafety evaluation and the rational design of nanomedicines in the future.
Lysophosphatidic acid (LPA) as the biomarker of early stage ovarian cancer is essentially difficult to detect due to lack of target spots. A dually crosslinked supramolecular hydrogel (DCSH) was developed to achieve sensing of LPA, which acts as a competitive guest molecule triggering the responsive crosslinking of the DCSH. Through this strategy, the surface plasmon resonance combined with optical waveguide spectroscopy could be used to quantitatively detect LPA with a responsive range covering physiological conditions (in pure form as well as mimicking LPA plasma solution) with high selectivity and sensitivity. LPA efficiently immerses into the host molecule β-cyclodextrin (β-CD) up to a 1:2 ratio by the competitive interaction mechanism, confirmed by one-dimensional nuclear overhauser effect spectroscopy (1D NOESY), highresolution mass spectrometry (HRMS), isothermal titration calorimetry (ITC), and computational simulation. Our method opens a new strategy to detect biomarkers without target spots and provides a platform for surface plasmon resonance (SPR)-based sensors measuring small molecules.
Photodynamic therapy (PDT) exhibits great potential for cancer therapy, but still suffers from nonspecific photosensitivity and poor penetration of photosensitizer. Herein, a smart perylene monoimide‐based nanocluster capable of enzyme‐triggered disassembly is reported as an activatable and deeply penetrable photosensitizer. A novel carboxylesterase (CE)‐responsive tetrachloroperylene monoimide (P1) was synthesized and assembled with folate‐decorated albumins into a nanocluster (FHP) with a diameter of circa 100 nm. Once P1 is hydrolyzed by the tumor‐specific CE, FHP disassembles into ultrasmall nanoparticles (ca. 10 nm), facilitating the deep tumor penetration of FHP. Furthermore, such enzyme‐triggered disassembly of FHP leads to enhanced fluorescence intensity (ca. 8‐fold) and elevated singlet oxygen generation ability (ca. 4‐fold), enabling in situ near‐infrared fluorescence imaging and promoted PDT. FHP permits remarkable tumor inhibition in vivo with minimal side effects through imaging‐guided, activatable, and deep PDT. This work confirms that this cascaded multifunctional control through enzyme‐triggered molecular disassembly is an effective strategy for precise cancer theranostics.
Gaseous formaldehyde (FA), a common indoor pollutant, presents a serious threat to human health. As an efficient tool for FA detection, fluorescent probes exhibit the advantages of low cost, ease of use, facile operation, etc. However, previously developed FA fluorescent probes are mostly based on fluorophores with aggregation-caused quenching features and thus require dispersion in solvent to detect FA. In this study, a fluorescent probe (TPE-FA) based on an aggregation-induced emission (AIE) fluorophore (tetraphenylethylene) has been developed for facile detection of gaseous FA through a fluorescence "turn-on" response. TPE-FA reacts with FA through 2-aza-Cope sigmatropic rearrangement. Based on the AIE features of TPE-FA, we fabricated a portable solid sensor, FA test plate, by directly loading TPE-FA on high performance thin-layer chromatography silica gel plate. The FA test plate achieved sensitive, selective, and quantitative detection of gaseous FA. The detection limit (0.036 mg/m 3 ) of the FA test plate is lower than the air quality guideline value of gaseous FA (0.1 mg/m 3 ) recommended by WHO. As a solid sensor for gaseous FA, the FA test plate based on AIE molecule is portable, which enables safer and more convenient use and transport compared to solution-based sensors.
Phototheranostics provide a safe, effective, and noninvasive way for the diagnosis and treatment of contemporary diseases, and organic dyes play a vital role. For example, chemical modification endowed dyes with powerful reactive oxygen species or heat generation ability, favoring for photodynamic therapy and photoacoustic (PA) imaging guided photothermal therapy (PTT) of serious diseases. Therefore, photophysical properties manipulation of dyes has become the focus in current dye chemistry research. The development of aggregate science has made great effort to solve this problem. In recent years, a large number of studies have focused on molecular aggregation behavior and its effect on photophysical performance. The most famous example is the discovery of aggregation‐induced emission (AIE) phenomenon. Based on AIE theory, more theories for revealing the relationship between molecular aggregation behavior and photophysical properties were proposed and elucidated. The photophysical property changes caused by dye aggregation have become a unique discipline, guiding the development of molecular science and material science. With the help of molecular self‐assembly, controllable aggregation of dyes can be realized, and stable nano‐theranostic reagents can be obtained. Furthermore, constructing dye assemblies with various photophysical properties will greatly reduce the cost of theranostic reagents, thus, expanding biomedical applications of organic dyes. Therefore, this review focuses on the photophysical characteristic changes caused by dye aggregation and their biological applications including, fluorescence/phosphorescence/PA imaging as well as photodynamic and PTT. This review will provide guidance for the design of organic dyes, the development of controllable aggregation methods, and the construction of multifunctional phototheranostic reagents.
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