Smart Free-Standing Bilayer Polyacrylamide/DNA Hybrid Hydrogel Film-Based Sensing System Using Changes in Bending Angles as a Visual Signal Readout.

Stimuli-responsive DNA hydrogels have shown great potential in sensing applications due to their attractive properties such as programmable target responsiveness, excellent biocompatibility, and biodegradability. In contrast to the extensively developed DNA hydrogel sensing systems based on the stimuli-responsive hydrogel-to-solution phase transition of the hydrogel matrix, the quantitative sensing application of DNA hydrogels exhibiting smart shape deformations has rarely been explored. Moreover, bulk DNA hydrogel-based sensing systems also suffer from high material cost and slow response. Herein, free-standing bilayer polyacrylamide/DNA hybrid hydrogel films with programmable responsive properties directed by the sequence of functional DNA units have been constructed. Compared with bulk DNA hydrogels, these DNA hydrogel films with a thickness at the micrometer scale not only greatly reduce the consumption of DNA materials but also facilitate the mass transfer of biomacromolecular substances within the hydrogel network, thus favoring their sensing applications. Therefore, a target-responsive smart DNA hydrogel film-based sensor system is further demonstrated based on the large amplitude macroscopic shape deformation of the film as a visual signal readout. As a proof of concept, Pb2+ or UO22+ ion-responsive DNA units were introduced into the active layer of the bilayer hydrogel films. In the presence of Pb2+ or UO22+ ions, the occurrence of a cleavage reaction within the DNA units leads to the release of DNA segments from the hydrogel film, inducing a dramatic shape deformation of the film, and thus sensing of Pb2+ or UO22+ ions with high specificity is achieved based on measuring the bending angle changes of these smart free-standing films. These smart DNA hydrogel film sensors with target-programmable responsiveness, simple operation, and ease of storage may hold promise for future rapid on-site testing applications.

Liquid Metal Nanocores Initiated Construction of Smart DNA-Polymer Microgels with Programmable and Regulable Functions and Near-Infrared Light-Driven Locomotion.

Due to their sequence-directed functions and excellent biocompatibility, smart DNA microgels have attracted considerable research interest, and the combination of DNA microgels with functional nanostructures can further expand their applications in biosensing and biomedicine. Gallium-based liquid metals (LMs) exhibiting both fluidic and metallic properties hold great promise for the development of smart soft materials; in particular, LM particles upon sonication can mediate radical-initiated polymerization reactions, thus allowing the combination of LMs and polymeric matrix to construct "soft-soft" materials. Herein, by forming active surfaces under sonication, LM nanoparticles (LM NPs) initiated localized radical polymerization reactions allow the combination of functional DNA units and different polymeric backbones to yield multifunctional core/shell microgels. The localized polymerization reaction allows fine control of the microgel compositions, and smart DNA microgels with tunable catalytic activities can be constructed. Moreover, due to the excellent photothermal effect of LM NPs, the resulting temperature gradient between microgels and surrounding solution upon NIR light irradiation can drive the oriented locomotion of the microgels, and remote control of the activity of these smart microgels can be achieved. These microgels may hold promise for various applications, such as the development of in vivo and in vitro biosensing and drug delivery systems.

Extracellular vesicle-encapsulated microRNA-296-3p from cancer-associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways.

Cancer-associated fibroblasts (CAFs), as important components of the tumor microenvironment, can regulate intercellular communication and tumor development by secreting extracellular vesicles (EVs). However, the role of CAF-derived EVs in ovarian cancer has not been fully elucidated. Here, using an EV-microRNA sequencing analysis, we reveal specific overexpression of microRNA (miR)-296-3p in activated CAF-derived EVs, which can be transferred to tumor cells to regulate the malignant phenotypes of ovarian cancer cells. Moreover, overexpression of miR-296-3p significantly promotes the proliferation, migration, invasion, and drug resistance of ovarian cancer cells in vitro, as well as tumor growth in vivo, while its inhibition has the opposite effects. Further mechanistic studies reveal that miR-296-3p promotes ovarian cancer progression by directly targeting PTEN and SOCS6 and activating AKT and STAT3 signaling pathways. Importantly, increased expression of miR-296-3p encapsulated in plasma EVs is closely correlated with tumorigenesis and chemoresistance in patients with ovarian cancer. Our results highlight the cancer-promoting role of CAF-derived EVs carrying miR-296-3p in ovarian cancer progression for the first time, and suggest that miR-296-3p encapsulated in CAF-derived EVs could be a diagnostic biomarker and therapeutic target for ovarian cancer.

Solar-powered simultaneous highly efficient seawater desalination and highly specific target extraction with smart DNA hydrogels.

Obtaining freshwater and important minerals from seawater with solar power facilitates the sustainable development of human society. Hydrogels have demonstrated great solar-powered water evaporation potential, but highly efficient and specific target extraction remains to be expanded. Here, we report the simultaneous highly efficient seawater desalination and specific extraction of uranium with smart DNA hydrogels. The DNA hydrogel greatly promoted the evaporation of water, with the water evaporation rate reached a high level of 3.54 kilograms per square meter per hour (1 kilowatt per square meter). Simultaneously, uranyl-specific DNA hydrogel exhibited a high capture capacity of 5.7 milligrams per gram for uranium from natural seawater due to the rapid ion transport driven by the solar powered interfacial evaporation and the high selectivity (10.4 times over vanadium). With programmable functions and easy-to-use devices, the system is expected to play a role in future seawater treatment.

Macrophage Membrane-Reversibly Cloaked Nanotherapeutics for the Anti-Inflammatory and Antioxidant Treatment of Rheumatoid Arthritis.

During rheumatoid arthritis (RA) development, over-produced proinflammatory cytokines represented by tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) represented by H2 O2 form a self-promoted cycle to exacerbate the synovial inflammation and tissue damage. Herein, biomimetic nanocomplexes (NCs) reversibly cloaked with macrophage membrane (RM) are developed for effective RA management via dual scavenging of TNF-α and ROS. To construct the NCs, membrane-penetrating, helical polypeptide first condenses TNF-α siRNA (siTNF-α) and forms the cationic inner core, which further adsorbs catalase (CAT) via electrostatic interaction followed by surface coating with RM. The membrane-coated NCs enable prolonged blood circulation and active joint accumulation after systemic administration in Zymosan A-induced arthritis mice. In the oxidative microenvironment of joints, CAT degrades H2 O2 to produce O2 bubbles, which shed off the outer membrane layer to expose the positively charged inner core, thus facilitating effective intracellular delivery into macrophages. siRNA-mediated TNF-α silencing and CAT-mediated H2 O2 scavenging then cooperate to inhibit inflammation and alleviate oxidative stress, remodeling the osteomicroenvironment and fostering tissue repair. This study provides an enlightened strategy to resolve the blood circulation/cell internalization dilemma of cell membrane-coated nanosystems, and it renders a promising modality for RA treatment.

Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy.

BACKGROUND: Melatonin (MEL), an endogenous hormone, has been widely investigated in neurological diseases. Microglia (MG), a resident immunocyte localizing in central nervous system is reported to play important functions in the animal model of temporal lobe epilepsy (TLE). Some evidence showed that MEL influenced activation of MG, but the detailed model of action that MEL plays in remains uncertain. METHODS: In this study, we established a model of TLE in mice by stereotactic injection of kainic acid (KA). We treated the mice with MEL. Lipopolysaccharide, ROCK2-knockdown (ROCK-KD) and -overexpression (ROCK-OE) of lentivirus-treated cells were used in cell experiments to simulate an in vitro inflammatory model. RESULTS: The results of electrophysiological tests showed that MEL reduced frequency and severity of seizure. The results of behavioral tests indicated MEL improved cognition, learning, and memory ability. Histological evidences demonstrated a significant reduction of neuronal death in the hippocampus. In vivo study showed that MEL changed the polarization status of MG from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype by inversely regulating the RhoA/ROCK signaling pathway. In cytological study, we found that MEL had a significant protective effect in LPS-treated BV-2 cells and ROCK-KD cells, while the protective effect of MEL was significantly attenuated in ROCK-OE cells. CONCLUSION: MEL played an antiepileptic role in the KA-induced TLE modeling mice both in behavioral and histological levels, and changed MG polarization status by regulating the RhoA/ROCK signaling pathway.

Ultrasmall zirconium carbide nanodots for synergistic photothermal-radiotherapy of glioma.

Glioma is characterized by highly invasive, progressive, and lethal features. In addition, conventional treatments have been poorly effective in treating glioma. To overcome this challenge, synergistic therapies combining radiotherapy (RT) with photothermal therapy (PTT) have been proposed and extensively explored as a highly feasible cancer treatment strategy. Herein, ultrasmall zirconium carbide (ZrC) nanodots were successfully synthesized with high near-infrared absorption and strong photon attenuation for synergistic PTT-RT of glioma. ZrC-PVP nanodots with an average size of approximately 4.36 nm were prepared by the liquid exfoliation method and modified with the surfactant polyvinylpyrrolidone (PVP), with a satisfactory absorption and photothermal conversion efficiency (53.4%) in the near-infrared region. Furthermore, ZrC-PVP nanodots can also act as radiosensitizers to kill residual tumor cells after mild PTT due to their excellent photon attenuating ability, thus achieving a significant synergistic therapeutic effect by combining RT and PTT. Most importantly, both in vitro and in vivo experimental results further validate the high biosafety of ZrC-PVP NDs at the injected dose. This work systematically evaluates the feasibility of ZrC-PVP NDs for glioma treatment and provides evidence of the application of zirconium-based nanomaterials in photothermal radiotherapy.

Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury.

Myocardial ischemia reperfusion (IR) injury is closely related to the overwhelming inflammation in the myocardium. Herein, cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species (ROS)-ultrasensitive co-delivery of dexamethasone (Dex) and RAGE small interfering RNA (siRAGE) to attenuate myocardial inflammation. PPTP, a ROS-degradable polycation based on PGE2-modified, PEGylated, ditellurium-crosslinked polyethylenimine (PEI) was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles (MSNs), which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage. Upon intravenous injection to IR-injured rats, the nanotherapeutics could be efficiently transported into the inflamed cardiomyocytes via PGE2-assisted recognition of over-expressed E-series of prostaglandin (EP) receptors on the cell membranes. Intracellularly, the over-produced ROS degraded PPTP into small segments, promoting the release of siRAGE and Dex to mediate effective RAGE silencing (72%) and cooperative antiinflammatory effect. As a consequence, the nanotherapeutics notably suppressed the myocardial fibrosis and apoptosis, ultimately recovering the systolic function. Therefore, the current nanotherapeutics represent an effective example for the co-delivery and on-demand release of nucleic acid and chemodrug payloads, and might find promising utilities toward the synergistic management of myocardial inflammation. Electronic Supplementary Material: Supplementary material (experimental methods, RNA and primer sequences, 1H NMR spectra, FTIR spectrum, TEM images, zeta potential, drug loading content, RNA and drug release, cytotoxicity, etc.) is available in the online version of this article at 10.1007/s12274-022-4553-6.

FAPhigh α-SMAlow cancer-associated fibroblast-derived SLPI protein encapsulated in extracellular vesicles promotes ovarian cancer development via activation of PI3K/AKT and downstream signaling pathways.

Ovarian cancer is the most lethal gynecological malignancy worldwide with high metastasis and poor prognosis rates. Cancer-associated fibroblasts (CAFs), a heterogeneous population of cells that constitutes a major component of the tumor microenvironment, secrete extracellular vesicles (EVs) loading with proteins, lipids, and RNAs to promote tumorigenesis. However, the specific roles of CAF-derived proteins contained in EVs in ovarian cancer remain poorly understood at present. Using the gene expression microarray analysis, we identified a list of dysregulated genes between the α-SMA+ CAF and FAP+ CAF subpopulations, from which secretory leukocyte protease inhibitor (SLPI) was chosen for further validation. Quantitative PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assays were used to assess SLPI expression in ovarian cancer cells, tissues, CAFs, and EVs. Additionally, we evaluated the effects of exogenous SLPI on proliferation, migration, invasion, and adhesion of ovarian cancer cells in vitro. Our results showed SLPI protein was upregulated in CAFs, particularly in the FAPhigh α-SMAlow CAF subpopulation, and associated with increased tumor grade and decreased overall survival (OS). Importantly, CAF-derived SLPI protein could be encapsulated in EVs for delivery to ovarian cancer cells, thus facilitating cell proliferation, migration, invasion, and adhesion via activating the PI3K/AKT and downstream signaling pathways. Moreover, high plasma expression of SLPI encapsulated in EVs was closely correlated with tumor stage in ovarian cancer patients. Our collective results highlight an oncogenic role of plasma EV-encapsulated SLPI secreted by CAFs in tumor progression for the first time, supporting its potential utility as a prognostic biomarker of ovarian cancer.

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood-brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.

Cytokine-scavenging nanodecoys reconstruct osteoclast/osteoblast balance toward the treatment of postmenopausal osteoporosis.

Imbalance between osteoblasts and osteoclasts accounts for the incidence and deterioration of postmenopausal osteoporosis. Abnormally elevated RANKL and TNF-α levels after menopause promote osteoclast formation and inhibit osteoblast differentiation, respectively. Here, nanodecoys capable of scavenging RANKL and TNF-α were developed from preosteoclast (RAW 264.7 cell) membrane­coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which inhibited osteoporosis and maintained bone integrity. The nanodecoys effectively escaped from macrophage capture and enabled prolonged blood circulation after systemic administration. The abundant RANK and TNF-α receptor (TNF-αR) on the cell membranes effectively neutralized RANKL and TNF-α to prevent osteoclastogenesis and promote osteoblastogenesis, respectively, thus reversing the progression of osteoporosis in the ovariectomized (OVX) mouse model. These biomimetic nanodecoys provide an effective strategy for reconstructing the osteoclast/osteoblast balance and hold great potentials for the clinical management of postmenopausal osteoporosis.

A near-infrared light-controlled, oxygen-independent radical generating nano-system toward cancer therapy.

Anti-tumor treatment based on free radicals is often inefficient in hypoxic tumors, mainly because of the oxygen-dependent generation mechanism of reactive oxygen species (ROS). Herein, we report an NIR laser-controlled nano-system that is capable of generating alkyl radicals in situ in an oxygen-independent approach. Hollow mesoporous Prussian blue nanoparticles (HPB NPs) were developed to co-encapsulate the azo initiator (AIBI) and 1-tetradecanol as the phase change material (PCM, melting point of ∼39 °C), obtaining the AP@HPB NPs. At normal body temperature, the PCM remained in the solid state to prevent the pre-leakage of AIBI. Upon NIR laser irradiation (808 nm) at the tumor site, AP@HPB NPs generated heat upon photothermal conversion, which melted the PCM to release AIBI and decomposed AIBI to produce toxicity free alkyl radicals under both normoxic and hypoxic conditions. The alkyl free radicals efficiently killed tumor cells by causing oxidative stress and damaging DNA. Meanwhile, NIR light-induced hyperthermia cooperated with free radicals to efficiently eradicate tumors. This study therefore provides a promising strategy toward oxygen-independent free radical therapy, especially for the treatment of hypoxic tumors.

S100A11 Promotes Glioma Cell Proliferation and Predicts Grade-Correlated Unfavorable Prognosis.

The prognosis of glioma is significantly correlated with the pathological grades; however, the correlations between the prognostic biomarkers with pathological grades have not been elucidated. S100A11 is involved in a variety of malignant biological processes of tumor, whereas its biological and clinicopathological features on glioma remain unclear. In this study, the S100A11 expression and clinical information were obtained from the public databases (TCGA, GEPIA2) to analyze its correlations with the pathological grade and the prognosis of glioma patients. We then verified the expression of S100A11 by immunohistochemistry staining. The effects of S100A11 on the proliferation of glioma cells were confirmed by cytological function assays (CCK-8, Flow cytometry, Clone formation assay) in vitro, the role of S100A11 in regulation of glioma growth was determined by xenograft model assay. We observed that S100A11 expression positively correlated with the pathological grades, while negatively correlated with the survival time of patients. In cytological analysis, we found the proliferations of glioma cell lines were significantly inhibited in vitro (P < 0.05) after interfering S100A11 expression via shRNAs. The cell cycle was blocked at G0/G1 stage. The ability of clone formation was significantly decreased, and the tumorigenicity in vivo was weakened (P < 0.05). In summary, S100A11 was over-expressed in gliomas and positively correlated with the pathological grades. Interfering the expression of S100A11 significantly inhibited the proliferation of glioma in vitro and the tumorigenicity in vivo (P < 0.05). In conclusion, S100A11 might be considered as a potential biomarker in glioma.

Carbon nitride-doped melamine-silver adsorbents with peroxidase-like catalysis and visible-light photocatalysis: Colorimetric detection and detoxification removal of total mercury.

Mesoporous melamine-silver (MA-Ag) nanocomposites doped with carbon nitride quantum dots (CNQDs) were fabricated simply by the controlled supramolecular self-assembly. It was discovered that the resulting nanoflower-like CNQDs@MA-Ag nanocomposites could exhibit the peroxidase-like catalysis, which could be specifically enhanced by Hg2+ by forming Ag@Hg alloys. A double catalysis-based colorimetric method was thereby developed for the fast detecting of Hg2+ and Hg0 in wastewater samples, with the levels down to 0.050 nM and 18.3 nM, respectively. Moreover, strong visible-light-driven photocatalysis of the nanocomposites was demonstrated for oxidizing Hg0 into Hg2+ through photocatalytic H2O2 production so as to realize the detoxification of Hg0 in the environmental wastewater. Besides, the fabricated mesoporous CNQDs@MA-Ag nanocomposites with large specific surface areas might facilitate the high Hg adsorption through the powerful MA-Hg chelate interaction, showing the efficient adsorption and/or removal of total Hg. The catalysis-selective colorimetric analysis and photocatalysis-based detoxification removal of total mercury may promise for wide applications in the environmental monitoring and wastewater treatment of toxic heavy metals of mercury.

A fluorimetric testing strip for the visual evaluation of mercury in blood using copper nanoclusters with DMSO-enhanced fluorescence and stability.

A fluorimetric analytical method using test strips has been fabricated for detecting Hg2+ ions in blood by using copper nanoclusters (Cu NCs) prepared via a biomineralization route. Unexpectedly, the as-prepared Cu NCs displayed greatly amplified red fluorescence once dispersed in DMSO, the intensity of which decreased specifically in the presence of Hg2+. Moreover, the resultant Cu NCs were deposited onto test strips to be further fast dried on superhydrophobic substrates in vacuum. The test strip-based fluorimetry can allow for the direct analysis of Hg2+ in blood in the linear concentration range of 0.10-1000 nM. Importantly, this solvent-enhanced fluorescence protocol for different metal probes such as Cu NCs promises extensive analysis applications for designing numerous fluorimetric platforms such as test strips.

TUSC3 induces drug resistance and cellular stemness via Hedgehog signaling pathway in colorectal cancer.

Tumor suppressor candidate 3 (TUSC3) is a coding gene responsible for N-glycosylation of many critical proteins. TUSC3 gene plays an oncogenic role in colorectal cancer (CRC), however, the role of TUSC3 in drug resistance of CRC is still unclear. The aim of this study is to investigate the biological function and molecular mechanism of TUSC3 in CRC drug resistance. The expression of TUSC3 in CRC is positively correlated to tumor stage in 90 paired clinical samples, and negatively associated with overall survival and disease-free survival of CRC patients. In vitro, TUSC3 promotes the formation of stemness and induces the drug resistance to 5-fluorouracil and cis-dichlorodiammineplatinum(II) in CRC cells. The tissue microarray assay and bioinformatic analysis indicate that TUSC3 may promote the expression of CD133 and ABCC1 via Hedgehog signaling pathway. Treatment of Hedgehog signaling pathway agonist or inhibitor in TUSC3-silenced or TUSC3-overexpressed cells reverse the effects of TUSC3 in cellular stemness phenotype and drug resistance. Meanwhile, coimmunoprecipitation and immunofluorescence assays indicate a tight relationship between TUSC3 and SMO protein. Our data suggest that TUSC3 promotes the formation of cellular stemness and induces drug resistance via Hedgehog signaling pathway in CRC.

A selective colorimetric and efficient removal strategy for mercury (II) using mesoporous silver-melamine nanocomposites synthesized by controlled supramolecular self-assembly.

Mesoporous silver-melamine (Ag-MA) nanocomposites were synthesized by controlled supramolecular self-assembly with various structural morphologies. It was discovered that the rod-like Ag-MA nanocomposites could present the larger Hg2+-enhanced catalysis by forming Ag-Hg alloys. Also, they could display large surface-to-volume area and high aqueous stability for the selective Hg2+ enrichment and absorption of Hg2+ ions by yielding the stable coordination complexes. A catalysis-based colorimetric method was thus developed using 96-wells plates to probe Hg2+ ions in blood and wastewater with the linear Hg2+ concentrations ranging from 1.0 nM to 600 nM and 0.50 nM to 700 nM, respectively. Besides, mesoporous Ag-MA absorbents could facilitate the removal of Hg2+ ions in wastewater with the removal efficiency up to 99.76 % and the absorption capacity of 598.99 mg g-1.

Fe3O4 Nanozymes with Aptamer-Tuned Catalysis for Selective Colorimetric Analysis of ATP in Blood.

In this work, a simple and highly selective colorimetric method has been developed for quantifying trace-level ATP using Fe3O4 nanoparticles (Fe3O4 NPs). It was discovered that Fe3O4 NPs could present the dramatically enhanced catalysis once anchored with ATP-specific aptamers (Apts), which is about 6-fold larger than that of bare Fe3O4 NPs. In the presence of ATP, however, the Apts would be desorbed from Fe3O4 NPs due to the Apts-target binding event, leading to the decrease of catalysis rationally depending on ATP concentrations. A colorimetric strategy was thereby developed to facilitate the highly selective detection of ATP, showing the linear concentrations ranging from 0.50 to 100 µM. Subsequently, the developed ATP sensor was employed for the evaluation of ATP in blood with the analysis performances comparably better than those of the documented detection methods, showing the potential applications in the clinical laboratory for the detective diagnosis of some ATP-indicative diseases. Importantly, such a catalysis-based detection strategy should be extended to other kinds of nanozymes with intrinsic catalysis properties (i.e., peroxidase and oxidase-like activities), promising as a universal candidate for monitoring various biological species simply by using target-specific recognition elements like Apts and antibodies.

A selective colorimetric strategy for probing dopamine and levodopa through the mussel-inspired enhancement of Fe3O4 catalysis.

Mussel-inspired enhancement of Fe3O4 catalysis was discovered towards a highly selective and sensitive colorimetric strategy for the magnetic separation-based evaluation of dopamine and/or levodopa in urine, in which the specific interaction of bis-catechol-containing analytes and mesoporous Fe3O4 NPs would form highly stable complexes of bis-catechol-Fe coordination.

Q-graphene-scaffolded covalent organic frameworks as fluorescent probes and sorbents for the fluorimetry and removal of copper ions.

Metal-free fluorescent covalent organic frameworks (COFs) were synthesized initially with Q-Graphene (QG) scaffolds by the one-step covalent reactions of melamine-aldehyde and phenol-aldehyde poly-condensations using paraformaldehyde. It was discovered that onion-like hollow QG, which consists of multi-layer graphene and different carbon allotropes having a high proportion of folded edges and surface defects, could endow the scaffolded COFs with enhanced green fluorescence and environmental stability. Unexpectedly, they could exhibit the powerful absorption for Cu2+ ions resulting in the specific quenching of fluorescence. A fluorimetric strategy with QG-scaffolded COFs was thereby developed to probe Cu2+ ions separately in blood and wastewater with the linear concentration ranges of 0.0010-10.0 µM (limit of detection of 0.50 nM) and 0.0032-32.0 µM (limit of detection of 2.4 nM), respectively, promising the potential applications for the field-applicable monitoring of Cu2+ ions in the clinical and environmental analysis fields. In addition, the prepared COFs sorbents were employed to absorb Cu2+ ions in wastewater showing high removal efficiency. More importantly, such an one-pot fabrication route with hollow QG scaffolds may be tailorable extensively for the preparation of a variety of metal-free multifunctional COFs with enhanced fluorescence, water solubility, environmental stability, and metal removal capability.