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We unveil a rich solvation dynamics of water molecules at the hematite/liquid water interface spanning three different time scales. This is made possible through extensive hybrid DFT molecular dynamics simulations, accelerated by machine learning.

The biomimetic iron(ii)-hydroperoxo species prefers to decay to an oxo-iron(iv)-hydroxy one to exert substrate oxidations and ligand self-hydroxylation.

Bacillus subtilis are probiotic microbes that are difficult to formulate when they are not in their spore form. Using self-assembling coatings, these cells were successfully protected during the freeze-drying process.

The nonheme iron(IV)-oxido complex trans-N3-[(L1)FeIV=O(Cl)]+, where L1 is a derivative of the tetradentate bispidine 2,4-di(pyridine-2-yl)-3,7-diazabicyclo[3.3.1]nonane-1-one, has an S = 1 electronic ground state and is the most reactive nonheme iron model system known so far, of a similar order of reactivity as nonheme iron enzymes (C-H abstraction of cyclohexane, 90 °C (propionitrile), t1/2 = 3.5 sec). The reaction with cyclohexane selectively leads to chlorocyclohexane, but “cage escape” at the [(L1)FeIII-OH(Cl)]+ / cyclohexyl radical intermediate lowers the productivity. Ligand field theory is used herein to analyze the d-d transitions of [(L1)FeIV=O(X)]n+ (X = Cl, Br, MeCN) in comparison with the thoroughly characterized ferryl complex of tetramethylcyclam (TMC=L2; [(L2)FeIV=O(MeCN)]2+). The ligand field parameters and d-d transition energies are shown to provide important information on the triplet-quintet gap and its correlation with oxidation reactivity.

Municipalities in central Oklahoma, U.S.A. increasingly rely on water drawn from the Central Oklahoma Aquifer (COA) as surface water resources have not grown in proportion to population and current water demands. However, water drawn from certain regions of the COA frequently contains elevated levels of naturally occurring hexavalent chromium. Rock samples from the Norman Arsenic Test Hole Core (NATHC) were investigated to identify the mineralogic host(s) of Cr and mechanisms of Cr(VI) release

The activation of O(2) at thiolate–ligated iron(ii) sites is essential to the function of numerous metalloenzymes and synthetic catalysts. Iron–thiolate bonds in the active sites of nonheme iron enzymes arise from either coordination of an endogenous cysteinate residue or binding of a deprotonated thiol-containing substrate. Examples of the latter include sulfoxide synthases, such as EgtB and OvoA, that utilize O(2) to catalyze tandem S─C bond formation and S-oxygenation steps in thiohistidine biosyntheses. We recently reported the preparation of two mononuclear nonheme iron–thiolate complexes (1 and 2) that serve as structural active-site models of substrate-bound EgtB and OvoA (Dalton Trans. 2020, 49, 17745–17757). These models feature monodentate thiolate ligands and tripodal N(4) ligands with mixed pyridyl/imidazolyl donors. Here, we describe the reactivity of 1 and 2 with O(2) at low temperatures to give metastable intermediates (3 and 4, respectively). Characterization with multiple spectroscopic techniques (UV-vis absorption, NMR, variable-field and -temperature Mössbauer, and resonance Raman) revealed that these intermediates are thiolate-ligated iron(iii) dimers with a bridging oxo ligand derived from the four-electron reduction of O(2). Structural models of 3 and 4 consistent with the experimental data were generated via density functional theory (DFT) calculations. The combined experimental and computational results illuminate the geometric and electronic origins of the unique spectral features of diiron(iii)-μ-oxo complexes with thiolate ligands, and the spectroscopic signatures of 3 and 4 are compared to those of closely-related diiron(iii)-μ-peroxo species. Collectively, these results will assist in the identification of intermediates that appear on the O(2) reaction landscapes of iron–thiolate species in both biological and synthetic environments.

We report a facile and reversible method to immobilize a broad range of His6-tagged proteins on the E. coli cell surface through Fe(iii)-metal complexes. A His6-tagged eGFP and four His6-tagged enzymes were successfully immobilized on the cell surface. Additionally, a hydrogel sheath around E. coli cells was generated by immobilized His6-tagged HRP.

To reduce the side effect of paclitaxel and enhance accumulation at the tumor site, a novel redox-responsive nanovector with excellent biocompatibility based on disulfide-linked amphiphilic polymer and magnetic nanoparticle was prepared. The system would realize PTX release due to breakage of the disulfide bond when being targeted to the tumor site by the external magnetic field. The nanovector significantly improved endocytosis and enhanced accumulation at the tumor site, with an effective inhibition of tumor cells in vitro and in vivo.

Electrocatalysis is key to the development of several important energy and biosensing applications. In this regard, the crystalline phase-dependent electrocatalytic activity of materials has been extensively studied for reactions such as hydrogen evolution, oxygen reduction, etc. But such comprehensive studies for evaluating the phase-dependence of electrochemical biosensing have not been undertaken. Herein, three crystalline phases (α-, β-, and γ-) of iron oxyhydroxide (FeOOH) have been synthesized and characterized by spectroscopic and microscopy techniques. Electrochemical studies revealed their high sensitivity and selectivity towards dopamine (DA) detection. Amongst the three electrocatalysts, β-FeOOH shows the highest sensitivity (337.15 μA mM−1 cm−2) and the lowest detection limit (0.56 μM). The enhanced electrocatalytic activity of β-FeOOH, as compared to that of α- and γ-FeOOH, was attributed to its higher active site percentage and facile electrode kinetics. Furthermore, theoretical studies probed into the DA-FeOOH interactions by evaluating the charge transfer characteristics and hydrogen adsorption energies of the three phases to support the experimental findings.

Photodynamic therapy (PDT) provides an alternative option to root out localized triple-negative breast cancer (TNBC) and has been experiencing a surge of research interest over recent years. In this study, we put forward a paradigm of designing novel transition metal-based PSs with the following characteristics: favorable cell-permeability, significant light-harvesting ability and prominent ROS yield. A novel BODIPY-Ir(III) conjugate has been designed as a photoinduced ROS (1O2, ˙OH and ˙O2−) generator. BODIPY-Ir is highly photoactive in subduing cancer cells in the PDT regimen with PI values ranging from 172 to 519 and EC50 in the nanomolar regime. Among various cancerous cell lines, TNBC was especially sensitive to BODIPY-Ir-mediated PDT, with a stunning EC50 value of 4.32 nM (PI = 519) under a moderate flux of visible-light irradiation (500 nm, 10.5 mW cm−2). BODIPY-Ir mainly accumulates in mitochondria and induces cell apoptosis under irradiation. Furthermore, the nanomolar antiproliferative activity of BODIPY-Ir is retained under hypoxia (2.5% O2). This work sheds light on instilling the O2-independent type I mechanism and conferring a red-shift absorption to metal-based PSs which fundamentally facilitate the clinical translation of PSs.

Siderophore-mimicking macrocyclic peptoids were synthesized. Peptoid 3 with intramolecular hydrogen bonds showed an optimally arranged primary coordination sphere leading to a stable catecholate-iron complex. The tris(catecholato) structure of 3-Fe(iii) was determined with UV-vis, fluorescence, and EPR spectroscopies and DFT calculations. The iron binding affinity was comparable to that of deferoxamine, with enhanced stability upon air exposure.

Environmentally persistent free radicals (EPFRs) have drawn increasing attention. It is reported that EPFR formation is dependent on the presence of transition metals; however the size of the metal particles is ignored. In this study, we hypothesized that transition metals in smaller particle sizes could more efficiently promote the generation of EPFRs and thus have higher risks. Nanosized hematite (nanoHMT) and microsized hematite (microHMT) were studied and compared. We monitored the degradation of catechol and the generation of EPFRs under both dark and ultraviolet light conditions. Catechol degradation was inhibited in the presence of hematite in the dark, with more significant inhibition by nanoHMT. However, under ultraviolet light, catechol degradation was promoted by hematite, with more significant promotion by nanoHMT. The yield of free radicals in the nanoHMT system was always higher than that in the microHMT system. More dimers were detected in the nanoHMT system, which may have played an important role in stabilizing free radicals. More trivalent Fe was converted to divalent Fe in the nanoHMT system than in the microHMT system. The relatively more active sites for the catechol interaction promoted EPFR generation. These results highlighted that size-dependent reactions should be well considered when predicting the environmental behavior and risks of organic contaminants.

Nanoparticle-mediated photothermal therapy (PTT) is an emerging modality to treat tumors with both spatial and temporal control provided by light activation. Gold decorated iron oxide nanoflowers (GIONF) are good candidates for PTT due to their biocompatibility, biodegradability and light-to-heat conversion. Profound changes in the tumor immune environment might be early induced by the gold and iron oxide metallic agents in addition to the photothermal effects. This study aims to elucidate the outcome of GIONF on their own, and of GIONF-induced mild hyperthermia in the tumor immune infiltrate in a murine model of triple negative breast cancer. First we explored the effects of 24 h GIONF exposure on bone-marrow derived macrophages (BMDM), revealing significant effects on the BMDM phenotype and secretion, 6 days post-incubation, with important downregulation of several cytokines and MHCII expression, predominantly towards a pro-inflammatory response. Intratumoral administration of GIONF promoted an increase in monocyte recruitment at day 1 post-administration, shifting towards a pro-inflammatory anti-tumor microenvironment with lower Treg population and a 4 fold lower CD4/CD8 ratio compared to the control at day 12. On top of the GIONF effects, mild hyperthermia (43 °C for 15 min), although it does not induce significant changes in tumor growth, resulted in an additional increase of CD8+ T lymphocytes and pro-inflammatory cytokines. The combination of a timely controlled immune response to GIONF and to mild hyperthermia could be used as a remotely triggered adjuvant treatment to immunotherapy approaches at the best favorable time-window.

Among conventional cancer therapies, radio-frequency magnetic hyperthermia (MHT) has widely been investigated for use with magnetic nanoparticles (MNPs). However, the majority of in vivo biodistribution studies have tested very low MNP dosages (equivalent to magnetic resonance imaging (MRI) applications) to check for clearance rate; which is far below the clinical dose of MHT. Due to this poor validation in preclinical scenarios, quite a few MNPs already in clinical use were later discontinued, on grounds of unexpected clinical outcomes in terms of inflammation, and prolonged clearance in vivo. By exploiting an economical method of synthesis, we have developed chitosan-coated Fe3O4 nanoparticles with high heating efficiency performance. Their anti-tumor response was evaluated in an ectopic tumor model of C6 glioblastoma by MHT. The intratumoral injection of MNPs on days 1 and 7 resulted in rapid tumor inhibition rate of 69.4% within 8 days, with complete inhibition within 32 days, and no recurrence recorded over a 5-month follow-up. Notably, the MNP-mediated MHT therapy achieved the highest degree of therapeutic efficacy required for complete tumor ablation by combining controlled temperature range (

Pathological angiogenesis is a critical contributor to atherosclerotic plaque rupture. However, there are few effective theranostic strategies to stabilize plaques by suppressing neovascularization. In this study, we fabricated a polymeric nanosystem using 3 nm manganese ferrite (MnFe2O4) and perfluorohexane (PFH) stabilized by polylactic acid-glycolic acid (PLGA) shells and conjugated to the surface of an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody [ramucirumab (Ram)]. The PFH@PLGA/MnFe2O4-Ram nanoparticles (NPs) were used as atherosclerotic plaque angiogenesis theranostics for multimodal imaging-guided photothermal therapy (PTT). Three-nanometer MnFe2O4 is an excellent magnetic resonance imaging T1 and photoacoustic imaging contrast agent. Upon exposure to near-infrared (NIR) light, MnFe2O4 in the NPs could transform NIR light into thermal energy for the photothermal elimination of plaque angiogenesis. Additionally, optical droplet vaporization of PFH in the NPs triggered by the thermal effect to form gas bubbles enhanced ultrasound imaging. Our in vitro experiments revealed that PFH@PLGA/MnFe2O4-Ram NPs actively accumulated in rabbit aortic endothelial cells, and NP-mediated PTT promoted endothelial cell apoptosis while inhibiting their proliferation, migration, and tubulogenesis. Notably, the PFH@PLGA/MnFe2O4-Ram NPs possessed excellent photostability and biocompatibility. In the rabbit advanced atherosclerotic plaque model, PFH@PLGA/MnFe2O4-Ram NP-guided PTT significantly induced apoptosis of neovascular endothelial cells and improved the hypoxia status in the plaque 3 days after treatment. On day 28, PTT significantly reduced the density of neovessels and subsequently stabilized rabbit plaques by inhibiting plaque hemorrhage and macrophage infiltration. Collectively, these results suggest that PFH@PLGA/MnFe2O4-Ram NP-guided PTT is a safe and effective theranostic strategy for inhibiting atherosclerotic plaque angiogenesis.

A process for the α-carboxyalkylation of tryptophols and tryptamines by the functionalization of C-H bonds under visible light irradiation has been developed. The photochemical strategy activated the C-Br bonds of α-bromo-alkylcarboxylic esters to provide carbon-centered radicals under the catalysis of Ir(iii) photocatalyst and coupled with indole derivatives. This methodology displayed wide functional group tolerance and excellent regioselectivity, and was applied to the late-stage functionalization and preparation of indole-containing hybrids.

Magnetic iron oxide nanoparticles (IONPs) have wide applications in magnetic resonance imaging (MRI), biomedicine, drug delivery, hyperthermia therapy, catalysis, magnetic separation, and others. However, these applications are usually limited by irreversible agglomeration of IONPs in aqueous media because of their dipole-dipole interactions, and their poor stability. A protecting polymeric shell provides IONPs with not only enhanced long-term stability, but also the functionality of polymer shells. Therefore, polymer-grafted IONPs have recently attracted much attention of scientists. In this tutorial review, we will present the current strategies for grafting polymers onto the surface of IONPs, basically including "grafting from" and "grafting to" methods. Available functional groups and chemical reactions, which could be employed to bind polymers onto the IONP surface, are comprehensively summarized. Moreover, the applications of polymer-grafted IONPs will be briefly discussed. Finally, future challenges and perspectives in the synthesis and application of polymer-grafted IONPs will also be discussed.

The rigorous reaction conditions (sufficient H2O2 and a low pH value) of an efficient Fenton reaction limit its further biomedical translation. Therefore, it is urgent to improve the efficacy of the Fenton reaction at the tumor site for efficient ferroptotic therapy. Herein, a hypoxia-responsive-Azo-BSA functionalized biomimetic nanoreactor (Fe(iii)-GA/GOx@ZIF-Azo), encapsulating ultrasmall ferric-gallic acid coordination polymer nanoparticles (Fe(iii)-GA) and glucose oxidase (GOx) into a zeolitic imidazolate framework (ZIF), was constructed for tumor ablation through an intensive Fenton reaction accelerated by not only sustained Fe2+ and H2O2 supply but also low pH and photothermal stimulation. Moreover, Azo achieved charge reversal in a hypoxia microenvironment caused by the sustained oxygen consumption by GOx, which resulted in selective and enhanced tumor accumulation based on the hypoxia-activated positive feedback cellular uptake. This rationally designed biomimetic nanoreactor might lay a foundation for the clinical translation of ferroptotic therapy.

We herein report a new biological consequence from a unique interaction between nanoparticles of ferric-tannic complexes (Fe-TA NPs) and liver cancer cells (HepG2.2.15). The Fe-TA NPs were found to accumulate into the cells via specific cellular uptake mechanisms and thereafter disturbed cellular autophagy and cellular pH homeostasis, which led the cells to undergo autophagic stress and eventual death. According to biophysical analysis, the cells undergoing autophagic stress were found to lose their capability of attachment, migration, and movement. Similarly, KEGG analysis demonstrated the down-regulation of TGF-beta indicating that the autophagic stress is capable of reducing cancer cell invasion. Therefore, the Fe-TA NPs could be considered beneficial as a new pharmaceutical nanoplatform for liver cancer treatment via induction of autophagic stress.

Magnetic cobalt Ferrite nanoparticles capped with caprylate groups, CH3(CH2)6CO2−, have been synthesized using a novel non-hydrolytic coprecipitation method under inert conditions. Particle diameter was characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The spinel ferrite crystal phase was verified using X-ray diffraction (XRD), and the presence of the capping agent was confirmed using Fourier Transform Infrared spectroscopy (FTIR). Bactericidal effects of the particles were tested against broth cultures of Erwinia carotovora and Stenotrophomonas maltophilia. The final particles had an average diameter of 3.81 nm and readily responded to a neodymium magnet. The particles did have a significant effect on the OD600 of both broth cultures.

Bactericidal nanopillar arrays on cicada wings represent a non-toxic antimicrobial technology as they work through physical cell rupture instead of a chemical mechanism. Here, we reported iron-based nanopillar arrays (FeOOH and Fe2O3) that can grow on various substrates by a simple solution method. These surfaces showed good structure-based antimicrobial activity. Even more simply, we have prepared urchin-type FeOOH and Fe2O3 particles, which can be easily coated onto various substrates to create structure-based disinfection surfaces. This work provides a simple and general methodology to apply this killed-by-structure technology for real world uses.

Tumor necrosis factor (TNF-α) is capable of inducing apoptosis and is a promising candidate for genetic engineering drugs in cancer therapy; however, the serious side-effects of TNF-α hinder their clinical application. In the present study, a method for preparing fusion proteins of cell-penetrating peptides (CPP) and TNF-α (CTNF-α)-anchored exosomes coupled with superparamagnetic iron oxide nanoparticles (CTNF-α-exosome-SPIONs) with membrane targeting anticancer activity has been demonstrated. To acquire exosomes with TNF-α anchored in its membrane, a CTNF-α expression vector was constructed and a stable mesenchymal stem cell cell line that expressed CTNF-α was established. Conjugating transferrin-modified SPIONs (Tf-SPIONs) onto CTNF-α-exosomes through transferrin-transferrin receptor (Tf-TfR) interaction yields CTNF-α-exosome-SPIONs with good water dispersibility. The incorporation of TNF-α into exosomes and the conjugation of SPIONs significantly enhanced the binding capacity of TNF-α to its membrane-bound receptor TNFR I, thus increasing the therapeutic effects. CTNF-α-exosome-SPIONs significantly enhanced tumor cell growth inhibition via induction of the TNFR I-mediated apoptotic pathway. In vivo studies using murine melanoma subcutaneous cancer models showed that TNF-α-loaded exosome-based vehicle delivery enhanced cancer targeting under an external magnetic field and suppressed tumor growth with mitigating toxicity. Taken together, our results suggest that CTNF-α-exosome-SPIONs showed great potential in membrane targeting therapy.

Bioorthogonal reactions based on manipulating the physicochemical and biological behavior of natural cells have gained tremendous attention for meeting the demands for multifunctional microorganisms without decreasing cell viability. Described herein is a novel bioorthogonal method for microorganism (Aspergillus oryzae) modification which coats the microorganism with a photothermal conversion cloth for staying bioactive in cold environments. Two steps, including ferric ions primarily binding to the microorganism cell surface, followed by in situ polymerization of pyrrole, are adopted to actualize highly efficient polypyrrole modification on the microorganism surfaces. The production of α-amylase by Aspergillus oryzae and α-amylase catalytic ability are two representative indexes of cold adaptation as confirmed by a starch decomposition test. This strategy for coating microorganisms with photothermal cloth is biocompatible and cost-effective, and can achieve non-contact modulation, which also offers great promise for generating living cell-polymer hybrid structures based on other microorganism systems for low-temperature environmental adaptation.

Sorafenib (SF) is the first drug demonstrated to improve the survival of patients diagnosed with advanced-stage hepatocellular carcinoma (HCC). However, its clinical application is limited by the poor oral bioavailability and severe side effects. In this study, a multifunctional micellar nanodrug was developed for simultaneous HCC-targeted delivery of SF and tumor detection with magnetic resonance imaging (MRI). The micellar nanodrug incorporating SF and superparamagnetic iron oxide nanoparticles (SPIONs) was prepared from a diblock copolymer of monomethoxyl poly(ethylene glycol) and poly(N-(2-aminoethanethiol-co-2-aminoethyldiisopropylamine) aspartamide) and then decorated with anti-glypican-3 antibody (AbGPC3). Owing to the small size, weak positive charge and AbGPC3-mediated active targeting to HCC cells, the nanodrug exhibited an easy cellular uptake and enhanced tumor accumulation. The prominent reduction and pH dual-sensitivity allowed the nanodrug to rapidly release SF inside cancer cells via responding to the cytoplasmic glutathione and lysosomal acidity. The nanodrug not only significantly improved the anticancer effects of SF in hepatoma treatment but also facilitated a noninvasive tumor detection and monitoring of in vivo drug delivery by MRI, which revealed its great potential as a promising theranostic system.

An efficient and practical method has been developed for the synthesis of steroidal imidazoheterocycles via cost-effective and environmentally benign FeCl3-catalyzed oxidative amination. A library of steroidal imidazo[1,2-a]pyridines was directly synthesized from readily available 2-aminopyridines and steroidal ketones in aerobic conditions. The synthesized compounds were screened for activity on human microsomal cytochrome P450s CYP7, CYP17 and CYP21. Antiproliferative activity of two lead compounds 3ia and 3la was additionally evaluated against the human MCF-7 (breast cancer), SKOV3 (ovarian cancer), and 22Rv1 (prostate cancer) cell lines. Steroidal imidazo[1,2-a]pyridine 3la which is a substrate molecule for CYP17A1 with IC50 = 1.7 μM (MCF-7), 3.0 (SKOV3), and 6.0 μM (22Rv1) has proved to be more active than reference drug cisplatin.

Sustainably made, flexible and biocompatible composites, having environmentally friendly compositions and multifunctional capabilities, are promising materials for several emerging biomedical applications. Here, the development of flexible and multifunctional chitosan-based bionanocomposites with a mixed reduced graphene oxide-iron oxide (rGO-Fe3−xO4) filler is described. The filler is prepared by one-pot synthesis, ensuring good dispersibility of the Fe3−xO4 nanoparticles and rGO within the chitosan matrix during solvent casting. The resulting bionanocomposites present superparamagnetic response at room temperature. The antioxidant activity is 9 times higher than that of pristine chitosan. The mechanical properties of the films can be tuned from elastic (∼8 MPa) chitosan films to stiff (∼285 MPa) bionanocomposite films with 50% filler. The magnetic hyperthermia tests showed a temperature increase of 40 °C in 45 s for the 50% rGO-Fe3−xO4 film. Furthermore, the composites have no cytotoxicity to the nontumorigenic (HaCat) cell line, which confirms their biocompatibility and highlights the potential of these materials for biomedical applications, such as hyperthermia treatments.

Herein, cobalt-involved redox in a magnetically responsive drug-loaded nanocatalyst (PTX/Co-Lips@Fe3O4) was used to convert Fe(III) to Fe(II) for enhancing tumor ferrotherapy for the first time. Moreover, this work highlighted an “all in one” strategy: (1) targeting, chemotherapy, and ferrotherapy in one nanomedicine, and (2) a decrease in GSH quantity, increase in the quantity of efficient catalytic ions, and use of a magnetic field, all in one tumor ferrotherapy enhancement approach.

Theranostic agents that integrate diagnostic and therapeutic modalities have drawn extensive attention due to their ability to deliver real-time imaging-guided tumor treatment. Herein, a novel core-shell polydopamine (PDA)-based theranostic agent (PDA@TA-Fe) was fabricated via a two-step strategy. Upon 808 nm and 1064 nm laser irradiation, this agent exhibited high photothermal conversion efficiencies of 29% and 41%, respectively. After endocytosis into tumor cells, the TA-Fe shell of PDA@TA-Fe gradually disintegrated in the weakly acidic tumor microenvironment (TME), and released the TA as an acidity-activated reductant that could reduce Fe3+ to Fe2+. Subsequently, the generated Fe2+ reacted with H2O2 to generate toxic hydroxyl radicals (˙OH) via the Fenton reaction, which induced the apoptosis of tumor cells and achieved the chemodynamic therapy (CDT). The heat produced by photothermal therapy (PTT) accelerated the ˙OH generation to achieve a synergetic effect of CDT/PTT. In vivo tumor-xenograft imaging and therapeutic assays demonstrated obvious contrast enhancement at the tumor site in the T1/T2-weighted MR imaging and efficient tumor suppression achieved after the intravenous injection of this agent because of the enhanced permeation and retention (EPR) effect. This study offered a new strategy to design an "all-in-one" nanoplatform for T1/T2 MR imaging-guided synergistic cancer treatment of CDT/PTT.

Herein, iron-terpyridine complexes with the iron centers at different initial valence states were utilized as homogeneous catalysts for the degradation of phenol in water. The iron(iii)-terpyridine complex induced the formation of more high-valent iron-oxo centers and hydroxyl radicals than the iron(ii)-terpyridine complex, leading to a higher catalytic activity.

Nanoengineered vehicles have the potential to deliver cargo drugs directly to disease sites, but can potentially be cleared by immune system cells or lymphatic drainage. In this study we explore the use of magnetism to hold responsive particles at a delivery site, by incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) into layer-by-layer (LbL) microcapsules. Microcapsules with SPIONs were rapidly phagocytosed by cells but did not trigger cellular ROS synthesis within 24 hours of delivery nor affect cell viability. In a non-directional cell migration assay, SPION containing microcapsules significantly inhibited movement of phagocytosing cells when placed in a magnetic field. Similarly, under flow conditions, a magnetic field retained SPION containing microcapsules at a physiologic wall shear stress of 0.751 dyne cm-2. Even when the SPION content was reduced to 20%, the majority of microcapsules were still retained. Dexamethasone microcrystals were synthesised by solvent evaporation and underwent LbL encapsulation with inclusion of a SPION layer. Despite a lower iron to volume content of these structures compared to microcapsules, they were also retained under shear stress conditions and displayed prolonged release of active drug, beyond 30 hours, measured using a glucocorticoid sensitive reporter cell line generated in this study. Our observations suggest use of SPIONs for magnetic retention of LbL structures is both feasible and biocompatible and has potential application for improved local drug delivery.

Fluorescent and magnetic materials play a significant role in biosensor technology, enabling sensitive quantification and separations with applications in diagnostics, purification, quality control, and therapeutics. Here, we present a magneto-fluorescent biosensor/separations platform consisting of quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs) that are separately encapsulated in amphiphilic block co-polymer micelles conjugated to DNA or protein (i.e., single-stranded (ss) DNA derived from the mRNA of the tumor suppressor protein p53 or avidin protein). Analytes were detected via an aggregation sandwich assay upon binding of at least 1 QD and 1 SPION-containing micelle to result in a fluorescent/magnetic composite. Multiplexed isolation of protein and DNA biomolecules was demonstrated by using QDs of varying emission wavelength; QD fluorescence intensity could be correlated with analyte concentration. Sequential or parallel biomolecule separation was achieved by adding appropriately functionalized SPION-containing micelles and applying user-controlled magnetic fields via patterned magnetic disks and wires. QD fluorescence was used to continuously visualize analyte separation during this process. This QD/SPION platform is simple to use, demonstrates ∼10-16 M sensitivity in analyte detection (comparable to competing QD biosensors based on energy transfer) with specificity against 1 and 2 basepair mismatches in DNA detection, molecular separations capability in solutions of ∼10-10 M, and permits simultaneous or parallel, multiplexed separation of protein and DNA. Thus, this versatile platform enables self-assembly-based rapid, sensitive, and specific detection and separation of biomolecules, simultaneously and with real-time visualization. This technology demonstrates potential for nanoscale assembly, biosensing, and bioseparations.

Using ultrasound activating contrast agents to induce sonoporation is a potential strategy for effective lesion-targeted gene delivery. Previous reports have proven that submicron nanodroplets have a better advantage than microbubbles in that they can pass through tumor vasculature endothelial gaps by passive targeting; however, they cannot achieve an adequate dose in tumors to facilitate ultrasound-enhanced gene delivery. Additionally, a few studies focused on delivering macromolecular genetic materials (i.e. overexpression plasmid and CRISPR plasmid) have presented more unique advantages than small-molecular genetic materials (i.e. miRNA mimics, siRNA and shRNA etc.), such as enhancing the expression of target genes with long-term effectiveness. Thereby, we constructed novel plasmid-loadable magnetic/ultrasound-responsive nanodroplets, where superparamagnetic iron oxide nanoparticle dispersed perfluoropentane was encapsulated with lipids to which plasmids could be adhered, and branched polyethylenimine was used to protect the plasmids from enzymolysis. Furthermore, in vitro and in vivo studies were performed to verify the magnetic tumor-targeting ability of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets and focused ultrasound enhanced intracellular plasmid delivery. The plasmid-loadable magnetic/ultrasound-responsive nanodroplets, carrying 16-19 plasmids per droplet, had desirable diameters less than 300 nm, and integrated the merits of excellent magnetic targeting capabilities and phase transition sensitivity to focused ultrasound. Under programmable focused ultrasound exposure, the plasmid-loadable magnetic/ultrasound-responsive nanodroplets underwent a phase-transition into echogenic microbubbles and the subsequent inertial cavitation of the microbubbles achieved an ∼40% in vitro plasmid delivery efficiency. Following intravenous administration, T2-weighted magnet resonance imaging, scanning electron microscopy and inductively coupled plasma optical emission spectrometry of the tumors showed significantly enhanced intratumoral accumulation of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets under an external magnetic field. And a GFP ELISA assay and immunofluorescence staining indicated that focused ultrasound-induced inertial cavitation of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets significantly enhanced the intracellular delivery of plasmids within the tumor after magnet-assisted accumulation, while only lower GFP levels were observed in the tumors on applying focused ultrasound or an external magnet alone. Taken together, utilizing the excellent plasmid-loadable magnetic/ultrasound-responsive nanodroplets combined with magnetism and ultrasound could efficiently deliver plasmids to cancer cells, which could be a potential strategy for macromolecular genetic material delivery in the clinic to treat cancer.

In this paper, a new magnetic molecular imprinted polymer-cyclodextrin (MMIP-CD) material was prepared by connecting β-cyclodextrin (CD) on the surface of a magnetic molecular imprinted polymer (MMIP) and used for the rapid and specific adsorption of zearalenone (ZEN). By using warfarin as the virtual template molecule, tetraethyl orthosilicate (TEOS) as the crosslinking agent, and (3-aminopropyl) triethoxysilane (APTES) as the functional monomer, a MMIP was produced by surface imprinting technology. Sulfobutyl ether-β-cyclodextrin attached to the surface of the MMIP under heating conditions produced a new specific adsorption material with exceptional adsorption capacity and excellent selectivity for ZEN. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and TEM-mapping results showed that the prepared MMIP-CD had a uniform particle size of about 480 nm, and the molecularly imprinted layer was successfully wrapped on the surface of the nanoparticles with a thickness of about 50 nm, whereby the cyclodextrin was effectively attached to the surface of the MMIP. The adsorption mechanism of MMIP-CD was confirmed by kinetic adsorption and thermodynamic adsorption experiments, the maximum adsorption capacity was found to be about 30 mg g-1, and the adsorption equilibrium could be reached within 20 min. The value of IF (QMMIP-CD/QMNIP) is 4.642. This showed that compared with MNIP, MMIP-CD showed a greatly improved specific adsorption capacity of ZEN. Selective experiments proved that MMIP-CD effectively combined the advantages of MMIP and CD, enhancing the adsorption capacity together with reducing the disadvantages that MMIP cannot distinguish structural analogs and CD cannot identify hydrophobic compounds effectively. In actual sample testing, the limit of quantification (LOQ) and limit of detection (LOD) were 0.1 ng kg-1 and 0.3 ng kg-1, respectively. The stability and detection precision of this method were 0.98-2.76% and 1.67-3.88%, respectively. The results proved that MMIP-CD had good development potential in the field of selective adsorption of ZEN, and laid the foundation for follow-up research.

Dental caries is a global risk in terms of oral health in many schoolchildren and in a vast majority of adults. The primary factor for caries formation is the attachment of bacteria on the tooth surface to form an oral biofilm which generates acids to demineralize calcium and eventually cause tooth decay. Oral biofilm elimination is still a challenge because bacteria are embedded inside with the biofilm matrix protecting them, preventing the penetration of antibiotics or bactericides. Promising strategies for disrupting oral biofilms have been developed, including the use of natural enzymes to degrade the biofilm matrix and hydrogen peroxide to kill bacteria. Here we demonstrate a strategy that combines nanozymes with peroxidase-like activity and bacteria generating biogenic hydrogen peroxide to eliminate oral biofilms for caries treatment. By using a saliva-coated hydroxyapatite disc and sectioned human tooth to mimic the real oral environment, we analyze the influence of iron oxide nanozymes or iron sulfide nanozymes on a Streptococcus mutans biofilm in the presence of Streptococcus gordonii which can generate hydrogen peroxide. Bacterial viability assays and biofilm morphology characterization show that the combination of nanozymes and bacteria remarkably reduces the bacteria number (5 lg reduction) and biofilm matrix (85% reduction). Therefore, the combination of iron-based nanozymes and hydrogen peroxide-generating bacteria may provide a new strategy for oral biofilm elimination in dental caries treatment.

High-quality multimodal imaging requires exogenous contrast agents with high sensitivity, spatial-temporal resolution, and high penetration depth for the accurate diagnosis and surveillance of cancer. Herein, we design a highly efficient fluorescent and magnetic multimodal probe by doping fluorescent molecule 2-(4-bromophenyl)-3-(4-(4-(diphenylamino)styryl)phenyl)fumaronitrile (TB) with near-infrared (NIR) fluorescent emission (714 nm) and superparamagnetic iron oxide (SPIO) into a polystyrene-polyethylene glycol (PS-PEG) matrix to form TB/SPIO@PS-PEG nanoparticles (TSP NPs). The as-prepared TSP NPs exhibit red aggregation-induced emission (AIE) with a maximum wavelength at 655 nm and high fluorescence quantum yield (QY) of 14.6%, facilitating the improvement of sensitivity and signal-to-background ratio for fluorescence molecular imaging (FMI). Phase behavior investigation of the TB/SPIO@PS-PEG probe system by Flory-Huggins lattice theory elucidates the highly efficient fluorescence of the multimodal probe, originating from the poor miscibility between TB and SPIO. Meanwhile, the TSP NPs possess good superparamagnetism and relaxivity and can thus be used as appropriate magnetic contrast agents for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). In addition, the good biocompatibility and photostability of the TSP NPs make them suitable for long-term monitoring. In vivo fluorescence imaging results indicate that the TSP NPs can facilitate monitoring of subcutaneous tumor growth for more than 24 days in a real-time manner. Multimodal imaging consisting of FMI, MRI, and MPI reveals that TSP NPs can monitor a liver tumor in situ with almost unlimited depth in tissues and high temporal-spatial resolution. As a multimodal probe, the TSP NPs manifest obvious synergistic advantages of long-term monitoring and high penetration depth and hold great prospects in tumor imaging.

Synergistic cancer starvation/ROS-mediated/chemo-therapy is developed through a cascade reaction with enzyme glucose oxidase (GOX) modified on the surface of an Fe-based metal organic framework (MOF(Fe)) and drug camptothecin (CPT) loaded into the cavities of MOF(Fe). Once internalized by tumor cells, GOX catalyzes endogenous glucose into hydrogen peroxide (H2O2) and gluconic acid (H+) enabling starvation therapy through choking off energy (glucose) supply. Meanwhile, the acidic micro-environment of tumor enhanced by the generated H+ degrades the MOF(Fe) simultaneously releasing CPT for chemotherapy and Fe3+, catalyzing H2O2 into one of the strongest reactive oxygen species (ROS) ˙OH enabling ROS-mediated therapy. Both in vitro and in vivo results show remarkable tri-modal synergistic anticancer effects. This work may shed some light on the development of novel multi-modal cancer therapies without any external intervention.

The homeostasis process in the gut tissue of humans relies on intestinal bacteria. However, the intestine is a complex structural tissue with a huge superficial area, and thus the effective application of probiotics in the treatment of Crohn's disease (CD) is still challenging. Herein, we show the feasibility of probiotic target delivery and retention using magnetic iron oxide nanoparticle-internalized Roseburia intestinalis, which can be easily directed by a magnetic field in vitro and in vivo. Subsequently, the increased colonization of this core profitable flora not only resulted in a better therapy effect than traditional intragastric administration but also altered the bacterial composition, leading to a higher diversity in microbial taxa in rats with colitis. Our findings illustrate the exciting opportunities that nanotechnology offers for alternative strategies to modulate biological systems remotely and precisely, which represent a step towards the wireless magnetic manipulation of living biological entities in microbiology.

Recently, due to their properties of high surface-to-volume ratio, easy penetration of the blood-brain barrier and easily modified surfaces, nanoparticles (NPs) have been recognized as promising inhibitors for Alzheimer's disease (AD) diagnosis and therapy. However, to achieve clinical application, the design and synthesis of specific NPs with good biocompatibility and degradability still are the main focus of research. In this paper, EGCG-Fe(iii)/PVP (EFPP) NPs with ultra-small size and good biocompatibility were first fabricated by the coordination reaction between Fe3+, EGCG and PVP. The obtained EFPP NPs exhibited effective influence on the inhibition of Aβ40 fibrillation and disaggregation of existing Aβ40 fibrils. The inhibitory effect was mainly derived from the synergistic effect of the weak hydrophobicity from PVP and antioxidant activity of EGCG. With the advantages of easy synthesis, high stability in simulated body fluid, high performance towards the antifibrillation of Aβ40 and biodegradability, it is reasonable to consider that the as-prepared EFPP NPs have good application prospects in the treatment of AD.

A new heparin targeting delivery platform was developed based on iron oxide (Fe3O4) nanoparticles and polyethyleneimine (PEI) functionalized black phosphorus nanosheets (BP NSs). Both in and ex vivo studies suggested that this drug delivery platform (PEI/Fe3O4@BP NSs) possessed high heparin loading capacity (≈450%), accurate magnetic enrichment capacity, and good biocompatibility. With the aid of near-infrared (NIR) laser irradiation, this BP NS based delivery platform could further enhance the photothermal thrombolysis effect. Most importantly, the experiments in vivo confirmed that the proposed PEI/Fe3O4@BP NSs could considerably prolong the effective drug concentration duration of heparin. By which means, accurate, long-acting, and effective thromboprophylaxis could be accomplished with limited drug dosage, which could radically reduce the perniciousness of drug overdose.

Glioma, the most severe primary brain malignancy, has very low survival rates and a high level of recurrence. Nowadays, conventional treatments for these patients are suffering a similar plight owing to the distinctive features of the malignant gliomas, for example chemotherapy is limited by the blood-brain barrier while surgery and radiation therapy are affected by the unclear boundaries of tumor from normal tissue. In the present study, a novel superparamagnetic iron oxide (SPIO) nanoprobe for enhanced T2-weighted magnetic resonance imaging (MRI) was developed. A frequently used MRI probe, SPIO nanoparticles, was coated with a silica outer layer and for the first time was covalently modified with interleukin-6 receptor targeting peptides (I6P7) to promote transportation through the blood-brain barrier and recognition of low-grade gliomas. The efficiency of transcytosis across the blood-brain barrier was examined in vitro using a transwell invasion model and in vivo in nude mice with orthotopic low-grade gliomas. The targeting nanoprobe showed significant MRI enhancement and has potential for use in the diagnosis of low-grade gliomas.

Herein, novel dehydropeptide-based magnetogels, based on the hydrogelators Npx-L-Phe-Z-ΔAbu-OH, Npx-L-Trp-Z-ΔPhe-OH and Npx-L-Ala-Z-ΔPhe-Gly-L-Arg-Gly-L-Asp-Gly-OH and containing manganese ferrite nanoparticles (diameters around 20 nm), were prepared and characterized. TEM and FTIR measurements showed that the magnetogels maintained the fibrous structure of neat hydrogels, with fibres of ca. 20 nm average width (generally in the range 10–30 nm) and a few conformational changes relative to the neat hydrogels. The magnetogels were tested as nanocarriers for two potential fluorescent antitumor drugs: a thienopyridine derivative and the natural compound curcumin. FRET (Förster resonance energy transfer) from the aromatic moieties (energy donors) of gels to the fluorescent drugs (energy acceptors) and fluorescence anisotropy measurements confirmed the incorporation of both drugs into the magnetogel matrices. The transport of both drugs loaded into the magnetogels to membrane models (small unilamellar vesicles) was assessed by FRET between the fluorescent drugs and the dye Nile Red. The magnetogel possessing the RGD sequence was most promising for the delivery of the thienopyridine derivative, whereas three magnetogels were found to be suitable for the delivery of curcumin., This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2013) and CQUM (UID/QUI/00686/2016). FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowledged for funding under research projects PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020) and PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015). S.R.S.V. and A.R.O.R. acknowledge FCT for research grants under UID/FIS/04650/2013 funding. Authors gratefully acknowledge Dr L. M. Vieira for carrying out the FTIR measurements at the Infrared Spectroscopy Lab. of the Centre of Physics, Univ. Minho., info:eu-repo/semantics/publishedVersion

Magnetic nanomaterials have drawn ample attention in the field of biotechnology due to their excellent magnetic properties and biocompatibility. These materials have been widely used for exosome isolation, DNA separation, magnetic resonance imaging, and drug delivery. However, their application in cell isolation has been limited due to the lack of efficient antibody conjugation and instability in aqueous solutions. In this study, we produced hybrid maghemite nanorod/immuno-microgels with high capturing capacity for cell isolation and enumeration. Lepidocrocite (γ-FeOOH) and maghemite (γ-Fe2O3) nanorods with controlled morphology are synthesized using hydrolysis method. The effects of the different synthesis conditions on morphology, phase composition, and magnetic properties of lepidocrocite are studied to determine the best synthesis conditions. We coat the nanorods with chitosan and attach them to the poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM-AA) microgel through chemical bonding to form a nano/hybrid microstructure. Our results suggest that the hybrid magnetic microgels have more antibody binding capacity and higher cancer cell capturing rate compared to pristine maghemite nanorods. In addition, new cell magnetometery method was applied for cancer cell quantification after capturing step in which different magnetized labelled cells were correlated to the saturation magnetization. In this method, higher concentrations of the primary cell suspension resulted in more binding of the magnetic immuno-microgels to the cells which was shown as saturation magnetization drop in the microgel-cell complex.

The lack of suitable tools for the identification of potential drug leads from complex matrices is a bottleneck in drug discovery. Here, we report a novel method to screen complex matrices for new drug leads targeting transmembrane receptors. Using α3β4 nicotinic receptors as a model system, we successfully demonstrated the ability of this new tool for the specific identification and effective extraction of binding compounds from complex mixtures. The formation of cell-membrane coated nanoparticles was confirmed by transmission electron microscopy. In particular, we have developed a direct tool to evaluate the presence of functional α3β4 nicotinic receptors on the cell membrane. The specific ligand binding to α3β4 nicotinic receptors was examined through ligand fishing experiments and confirmed by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization mass spectrometry. This tool has a great potential to transform the drug discovery process focusing on identification of compounds targeting transmembrane proteins, as more than 50% of all modern pharmaceuticals use membrane proteins as prime targets.

Cancer is a global epidemic and is considered a leading cause of death. Various cancer treatments such as chemotherapy, surgery, and radiotherapy are available for the cure but those are generally associated with poor long-term survival rates. Consequently, more advanced and selective methods that have better outcomes, fewer side effects, and high efficacies are highly in demand. Among these is the use of superparamagnetic iron oxide nanoparticles (SPIONs) which act as an innovative kit for battling cancer. Low cost, magnetic properties and toxicity properties enable SPIONs to be widely utilized in biomedical applications. For example, magnetite and maghemite (Fe3O4 and γ-Fe2O3) exhibit superparamagnetic properties and are widely used in drug delivery, diagnosis, and therapy. These materials are termed SPIONs when their size is smaller than 20 nm. This review article aims to provide a brief introduction on SPIONs, focusing on their fundamental magnetism and biological applications. The quality and surface chemistry of SPIONs are crucial in biomedical applications; therefore an in-depth survey of synthetic approaches and surface modifications of SPIONs is provided along with their biological applications such as targeting, site-specific drug delivery and therapy.

A main feature of biofilms is the self-produced extracellular polymeric substances (EPSs) that act as a protective shield, preventing biocide penetration. We use magnetic iron oxide nanoparticles (MNPs) in combination with magnetic fields to damage the biofilm matrix and cause detachment. A Methicillin-resistant Staphylococcus aureus (MRSA) biofilm strain is used to demonstrate the efficacy of the methodology with different sizes and concentrations of MNPs under AC and DC applied field conditions. We achieve up to a nearly 5 log10 reduction in biofilm bacteria after treatment with 30 mg mL-1 of 11 nm MNPs using a magnetic field. The MNPs cause significant mechanical disruption to the matrix and lead to biofilm dispersal. In addition, using magnetic hyperthermia further affects biofilm damage.

Although various nanomaterials have been developed for cancer theranostics, there remains a key challenge for effective integration of therapeutic drugs and diagnostic agents into a single multicomponent nanoparticle via a simple and scalable approach. Moreover, the bottlenecks of nanoformulation in composition controllability, colloidal stability, drug loading capability and batch-to-batch repeatability currently still hinder the clinical translation of nanomedicine. Herein, we report a coordination-driven flash nanocomplexation (cFNC) process to achieve scalable fabrication of doxorubicin-based metal-phenolic nanoparticles (DITH) with a hyaluronic acid surface layer through efficient control of coordination reaction kinetics in a rapid turbulent mixing. The optimized DITH exhibited a small hydrodynamic diameter (84 nm), narrow size distribution, high drug loading capacity (26.6%), high reproducibility and pH-triggered drug release behaviors. The studies indicated that DITH significantly increased cellular endocytosis mediated by CD44+ receptor targeting and accelerated intracellular drug release owing to the sensitivity of DITH to environmental pH stimuli. Furthermore, guided by T1-weighted magnetic resonance (MR) imaging function endowed by ferric ions, DITH exhibited prolonged blood circulation, enhanced tumor accumulation, improved therapeutic performance and decreased toxic side effects after intravenous injection in a MCF-7 tumor-bearing mice model. These results confirmed that the developed DITH is a promising vehicle for cancer theranostic applications, and our work provided a new strategy to promote the development of translational nanomedicine.

Nanozymes (nanoparticles with enzyme-like properties) have attracted considerable attention in recent years owing to their intrinsic enzyme-like properties and broad application in the fields of ELISA based immunoassay and biosensing. Herein, we systematically investigate the influence of crystal phases (γ-Fe2O3 and α-Fe2O3) of mesoporous iron oxide (IO) on their peroxidase mimetic activity. In addition, we have also demonstrated the applicability of these mesoporous IOs as nanozymes for detecting the glucose biomarker with a limit of detection (LOD) of 0.9 μM. Mesoporous γ-Fe2O3 shows high nanozyme activities (and magnetism) toward the catalytic oxidation of chromogenic substances, such as 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)-ABTS, as well as for the colourimetric detection of glucose, compared to that of α-Fe2O3. We believe that this in-depth study of crystal structure based nanozyme activity will guide designing highly effective nanozymes based on iron oxide nanostructures for chemical sensing, biosensing and environmental remediation.

A novel electrochemical strategy for simple and facile synthesis of semicarbazide functionalized nitrogen-doped graphene quantum dots (N-GQDs) was reported, based on direct exfoliation and oxidation from graphite rods. The average diameter of the as-synthesized N-GQDs is about 20 nm, and their dispersion is bright yellow due to the rich nitrogen and oxygen functional groups on their surface. The N-GQD dispersion was further applied in the selective detection of ferric ions (Fe3+) based on the photoluminescence (PL) quenching of N-GQDs after adding Fe3+. The fluorescent sensor has a wide linear range of 0–200 μM and a detection limit of 0.87 μM, which is much lower than the maximum level (0.3 mg L−1, equivalent to 5.4 μM) of Fe3+ permitted in drinking water by the U.S. Environmental Protection Agency (EPA). Moreover, these novel N-GQDs exhibit much wider emission bands, which extend into the entire visible region, and emit three primary color fluorescence independently. This distinctive behavior of the as-prepared GQDs not only breaks the limitation that traditional reported GQDs only exhibit blue emission in the short-wavelength region, but may also provide a new research platform for further applications of GQDs in real environmental detection and biological imaging systems.

Carbon dots with different emission fluorescence have a great number of potential applications for various areas from in vitro imaging and biotherapy, due to the good biosafety of red fluorescent CDs, to efficient ion detection and photocatalysis, due to the excellent photoluminescence properties of blue fluorescent carbon dots. Traditional methods for the synthesis of full-spectrum carbon dots require 24 h of synthesis and complex column chromatography. In this paper, a facile and efficient microfluidic method to continuously synthesize small and uniform carbon dots with full-spectrum emission fluorescence is developed for the first time. The synthesis process could be reduced to 20 minutes. Through XPS analysis and DFT calculations, it is quantitatively revealed that the number of primary amino groups determines the energy gap of the carbon dots and thus determines the fluorescence emission wavelength of the carbon dots. Applications for precise Fe3+ detection and in vitro bio-imaging were successfully implemented, showing great potential application value of the carbon dots.