Carbon dots (CDs), a kind of carbon material discovered accidentally, exhibit unexpected advantages in fluorescence imaging/sensing such as photostability, biocompatibility, and low toxicity. For ...emerging theranostics, an interdiscipline created by integrating therapy and diagnostics, CDs are good candidates when they are combined with targeted chemo/gene/photodynamic/photothermal therapeutic moieties. Here, the development of CDs in nanomedicine is reviewed from their use as original imaging agents and/or drug carriers to multifunctional theranostic systems. Finally, the challenges and prospects of the next‐generation of CD‐based theranostics for clinical applications are also discussed.
Carbon dots (CDs) in nanomedicine are gradually developed from original imaging agents and/or drug carriers to smart multifunctional theranostic systems. In addition to having the common advantages of stability, biocompatibility, and low toxicity, CDs with special photothermal therapy/ photodynamic therapy capability are successfully exploited. This work addresses recent encouraging progress in the development of CD‐based multifunctional nanomedicinal agents in theranostics.
Endogenous gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H
2
S) have been demonstrated to perform significant physiological and pharmacological ...functions and are associated with various diseases in biological systems. In order to obtain a deeper insight into their roles and mechanisms of action, it is desirable to develop novel techniques for effectively detecting gaseous signaling molecules. Small-molecule fluorescent probes have been proven to be a powerful approach for the detection and imaging of biological messengers by virtue of their non-invasiveness, high selectivity, and real-time
in situ
detection capability. Based on the intrinsic properties of gaseous signaling molecules, numerous fluorescent probes have been constructed to satisfy various demands. In this perspective, we summarize the recent advances in the field of fluorescent probes for the detection of NO, CO and H
2
S and illustrate the design strategies and application examples of these probes. Moreover, we also emphasize the challenges and development directions of gasotransmitter-responsive fluorescent probes, hoping to provide a general implication for future research.
This perspective article aims to introduce the design principles and recognition strategies of small-molecule fluorescent probes which are applied for the detection of gas signaling molecules including NO, CO and H
2
S in biological systems.
Chemiluminescence, the generation of light through chemiexcitation as a result of chemical reactions, has emerged as a novel tool for bioimaging and therapy
in vivo
. Due to the elimination of ...external optical excitation, it can effectively avoid background autofluorescence existing in fluorescence techniques, providing extremely high signal-to-noise ratios and sensitivity in bioimaging. Furthermore,
in situ
emitted photons can replace traditional excitation light to construct chemiexcited photodynamic therapy or drug release systems for the monitoring and treatment of deeply seated diseases or tumors. In this tutorial review, we will focus on the recent advancements of chemiluminescent platforms based on luminophore substrates including luminol and its derivatives, cypridina luciferin analogs, peroxyoxalates, and dioxetanes, and systematically summarize the design principles, sensing mechanisms, and bioimaging and therapeutic applications of representative chemiluminescent probes as well as theranostic agents. Finally, the potential challenges and perspectives of chemiluminescent platforms for bioimaging and therapeutics are also discussed.
The current progress, design principles in bioimaging and therapeutic applications, and future perspectives of various chemiluminescent platforms are reviewed.
Mild chemical processes of various analytes and detection methods involving revolutionary strategies in the fields of analytical chemistry, biology and environmental sciences have been extensively ...developed. This
critical review
focuses on representative examples of mild chemical processes that can be used in fluorescent chemodosimeters for ion sensing (anions and cations). A systematisation according to the type of reaction mechanism is established. Numerous examples including extensions combined with catalytic and material sciences applicable in fluorescence imaging and water treatment are also discussed (151 references).
This
critical review
focuses on advances in various mild chemical processes that can form the basis of fluorescent chemodosimeters for anions and cations, as well as catalytic and material science application in fluorescence imaging and water treatment.
As traditional phototherapy agents, boron dipyrromethene (BODIPY) photosensitizers have attracted increasing attention due to their high molar extinction coefficients, high phototherapy efficacy, and ...excellent photostability. After being formed into nanostructures, BODIPY‐containing nano‐photosensitizers show enhanced water solubility and biocompatibility as well as efficient tumor accumulation compared to BODIPY molecules. Hence, BODIPY nano‐photosensitizers demonstrate a promising potential for fighting cancer. This review contains three sections, classifying photodynamic therapy (PDT), photothermal therapy (PTT), and the combination of PDT and PTT based on BODIPY nano‐photosensitizers. It summarizes various BODIPY nano‐photosensitizers, which are prepared via different approaches including molecular precipitation, supramolecular interactions, and polymer encapsulation. In each section, the design strategies and working principles of these BODIPY nano‐photosensitizers are highlighted. In addition, the detailed in vitro and in vivo applications of these recently developed nano‐photosensitizers are discussed together with future challenges in this field, highlighting the potential of these promising nanoagents for new tumor phototherapies.
Boron dipyrromethene (BODIPY) nano‐photosensitizers are equipped with enhanced water solubility, biocompatibility, and tumor accumulation via the enhanced permeability and retention (EPR) effect. In addition, their excellent photostability and large molar extinction coefficient in the near infrared (NIR) region ensure a special phototherapy effect toward tumors. This review focuses on the design and preparation of BODIPY containing nano‐photosensitizers for anticancer phototherapy.
Cysteine (Cys) and homocysteine (Hcy) are essential for maintaining the cellular redox homeostasis and play critical roles in pathological and physiological processes. The development of ...Cys/Hcy-specific responsive fluorescent probes that are independent of the surrounding environment, equipment, and abundant endogenous GSH is critical to accurately investigate the roles of Cys/Hcy in living biological systems. In this work, a novel ratiometric and mitochondria-anchored fluorescence chemosensor, PYR, was constructed on the basis of 4-methylphenol-substituted pyronin fluorophore. The probe exhibited ratiometric fluorescence emission (F 540 nm/F 620 nm) for the detection of Cys/Hcy with high selectivity, sensitivity (Cys, 22 nM; Hcy, 23 nM), rapid response (Cys, 5 min), and a merit enhancement of ratio fluorescent signal (Cys, 163-fold; Hcy, 125-fold). The probe showed excellent membrane permeability and was applied to visualize mitochondrial biothiols in living cells under H2O2-induced redox imbalance, kidney tissues with a penetration depth of 100 μm, and Daphnia magna model for the first time. The results demonstrate that PYR will provide a promising platform for the diagnosis of thiol-related diseases.
Hypoxia, a quite universal feature in most solid tumors, has been considered as the “Achilles’ heel” of traditional photodynamic therapy (PDT) and substantially impairs the overall therapeutic ...efficacy. Herein, we develop a near-infrared (NIR) light-triggered molecular superoxide radical (O2 –•) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O2 –• action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation. Photomediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O2), ENBS-B can generate considerable O2 –• through type I photoreactions, and partial O2 –• is transformed to high toxic OH· through SOD-mediated cascade reactions. These radicals synergistically damage the intracellular lysosomes, which subsequently trigger cancer cell apoptosis, presenting a robust hypoxic PDT potency. In vitro coculture model shows that, benefiting from biotin ligand, ENBS-B achieves 87-fold higher cellular uptake in cancer cells than normal cells, offering opportunities for personalized medicine. Following intravenous administration, ENBS-B is able to specifically target to neoplastic tissues and completely suppresses the tumor growth at a low light-dose irradiation. As such, we postulated this work will extend the options of excellent agents for clinical cancer therapy.
Targeting is one of the most important strategies for enhancing the efficacy of cancer photothermal therapy (PTT) and reducing damage to surrounding normal tissues. Compared with the traditional ...targeting approaches, the active targeting of breast cancer cells in PTT using chemotherapeutic drugs, such as tamoxifen (TAM), in combination with single‐molecule photothermal photosensitizers has superior selectivity and therapeutic effects. However, single‐molecule drug‐targeting photosensitizers for improved PTT efficacy are not widely reported. Accordingly, herein, a near‐infrared induced small‐molecule photothermal photosensitizer (CyT) is developed that actively targets the estrogen receptors (ERs) of breast cancer cells as well as targets mitochondria by structure‐inherent targeting. Cell uptake and cytotoxicity studies using different types of cells show that CyT enhances the efficiency of TAM‐based PTT by targeting ER‐overexpressing breast cancer cells and selectively killing them. In vivo experiments demonstrate that CyT can be used as a photothermal agent for fluorescence imaging‐guided PTT. More importantly, the intravenous injection of CyT results in better targeting and efficiency of tumor inhibition compared with that achieved with the TAM‐free control molecule Cy. Thus, the study presents an excellent small‐molecule photothermal agent for breast cancer therapy with potential clinical application prospects.
Cyanine dye small‐molecule organic photothermal photosensitizers with long‐wavelength absorption exhibit good synthetic flexibility and biocompatibility. Single molecule drug targeting photothermal photosensitizers that covalently connect to chemotherapeutic drug molecules represent a promising new strategy to improve the targeting ability of photothermal therapy (PTT). This manuscript focuses on designing and preparing targeting photosensitizer (CyT) for enhanced breast cancer PTT.
Lysosomal polarity affects the interaction activities between enzymes and substrates at the cellular level. Abnormal lysosomal polarity closely linked with disorders and diseases is worthy of ...attention. The first fluorescence probe, which can image polarity ratiometrically and detect lysosomal polarity quantitatively, is reported herein. The probe termed NOH can emit dual-peaks both in solvents (λem = 474, 552 nm) and in micro-environment. NOH exhibits the Boltzmann function response of the fluorescence intensity ratio to the polarity in a wide range and localizes at lysosomes specifically (Rr = 0.97). In the method of ratiometric fluorescence imaging with NOH, the variation of lysosomal polarity (Δf) can be directly discerned by the color changes. In virtue of ratiometric fluorescence imaging and the Boltzmann function relationship between the fluorescence intensity ratio and the polarity, lysosomal polarity in MCF-7 cells was calculated to be 0.224 and the polarity in the condition of lysosomal storage disorders (or cell death) could also be obtained. This probe will be a promising tool for studying lysosome-related physiological or pathological processes.
The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly ...using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).
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