Solvent and monomer regulation synthesis of core-shelled magnetic ß-cyclodextrin microporous organic network for efficient extraction of estrogens in biological samples prior to HPLC analysis.

The abnormal estrogens levels in human body can cause many side effects and diseases, but the quantitative detection of the trace estrogens in complex biological samples still remains great challenge. Here we reported the fabrication of a novel core-shell structured magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON) for rapid magnetic solid phase extraction (MSPE) of four estrogens in human serum and urine samples prior to HPLC-UV determination. The uniform spherical core-shell Fe3O4@CD-MONs was successfully regulated by altering the reactive monomers and solvents. The Fe3O4@CD-MONs owned high specific surface area, good hydrophobicity, large superparamagnetism, and abundant extraction sites for estrogens. Under optimal conditions, the proposed MSPE-HPLC-UV method provided wide linearity range (2.0-400 µg L-1), low limits of detection (0.5-1.0 µg L-1), large enrichment factors (183-198), less adsorbent consumption (3 mg), short extraction time (3 min), and good stability and reusability (at least 8 cycles). The established method had also been successfully applied to the enrichment and detection of four estrogens in serum and urine samples with a recovery of 88.4-105.1 % and a relative standard deviation of 1.0-5.9 %. This work confirmed the feasibility of solvent and monomer regulation synthesis of Fe3O4@CD-MON composites, and revealed the great prospects of magnetic CD-MONs for efficient enrichment of trace estrogens in complex biological samples.

Synthesis of crown ether-based microporous organic networks: A new type of efficient adsorbents for chlorophenols.

Microporous organic networks (MONs) are a booming class of functional materials in elimination of environmental pollutants. However, the limit varieties of MONs still restrict their broad applications. Here we report the synthesis of a novel type of crown ether (CE)-based MONs via the coupling between brominated 18-crown-6 ether and different aromatic alkynyls. The constructed CE-based MONs integrates the good conjugation property of MONs and the inherent host-guest binding sites of CE, allowing the ultrafast and efficient adsorption and removal of a typical environmental priority pollutant 2,4,6-trichlorophenol (2,4,6-TCP). The hydrophobic CE-based MONs can also address the recovery challenge of unstable discrete CE in most organic and inorganic solvents. All CE-based MONs displayed fast adsorption kinetics (< 3 min) and large adsorption capacities (229.1-341.7 mg g-1) for 2,4,6-TCP. The CE-based MONs also gave stable adsorption capacities for 2,4,6-TCP in pH range of 4.0-6.0, NaCl concentration of 0-40 mg L-1, HA concentration of 0-30 mg L-1, or H2O2 ratio of < 5 %. Density functional theory calculation, Fourier transform infrared and X-ray photoelectron spectra evaluation revealed adsorption process involved hydrophobic, π-π and hydrogen bonding interactions. The CE-based MONs also showed favorable reusability and good adsorption for other toxic chlorophenols. This work highlights the potential of CE-based MONs in contaminants elimination.

Covalent coupling fabrication of microporous organic network bonded capillary columns for gas chromatographic separation.

Microporous organic networks (MONs) have shown great promise in separation science recently. Exploring novel, simple and convenient strategy to fabricate MONs coated capillary columns for gas chromatography (GC) still remains challenging but desirable for the development of MONs in chromatographic separation. To extend the potential application of MONs in separation science and to further develop novel method for the fabrication of MONs-based capillary columns, here we demonstrate a novel covalent coupling strategy to fabricate uniform MONs bonded capillary columns for GC separation of position isomers and hydrocarbons. The bare capillary column was firstly modified with (3-bromopropyl)trimethoxysilane to provide bromine sites for coupling with alkynyl monomers. The amino- and hydroxyl-functionalized MONs (MON-NH2 and MON-OH) were then directly grown onto the inner wall of the brominated capillary columns via the covalent coupling between bromine and alkynyl groups. The uniform MON-NH2 and MON-OH bonded capillary columns were obtained and showed good resolution for GC separation of dichlorobenzene, chlorotoluene, bromotoluene, and propylbenzene position isomers and many other hydrocarbons including linear alkanes, alkylbenzenes, pinene isomers, cyclohexane and benzene, ketones and aldehydes. The MONs bonded capillary columns also owned good lifetime and precision for dichlorobenzene isomers with the relative standard deviations (RSDs) of 0.2-0.3%, 1.2-2.1%, and 1.7-2.5% for retention time, peak height and peak area, respectively. In addition, the fabricated MON-NH2 and MON-OH bonded capillary columns offered better resolution than commercial InertCap-1, InertCap-5, InertCap-1701 and InertCap-WAX capillary columns for the separation of chlorotoluene and bromotoluene position isomers. These results revealed the feasibility of covalent coupling strategy to fabricate MONs-based stationary phases in GC, highlighting the potential of MONs in separation science.

Dendrimer grafted persistent luminescent nanoplatform for aptamer guided tumor imaging and acid-responsive drug delivery.

Theranostic nano-drug delivery systems are promising candidates for early diagnosis and treatment of tumors. However, it is a great challenge to achieve accurate intracellular delivery and stimuli-responsive drug release with the enhanced anti-tumor effects and reduced side effects. Herein we report the fabrication of polyamide-amine (PAMAM) dendrimer grafted persistent luminescence nanoparticles (PLNPs) via in situ growth of PAMAM on the surface of PLNPs and its application in targeted bioimaging and drug delivery. The developed PLNPs-PAMAM possesses strong renewable near-infrared persistent luminescence for imaging and gives abundant terminal groups for further functionalization. Aptamer AS1411 coupled to the PLNPs-PAMAM surface can specifically bind to the over-expressed nucleolin on the membrane of tumor cells and improve the intracellular accumulation of the nanoparticles. Doxorubicin (DOX) is loaded on PLNPs-PAMAM by a pH-sensitive hydrazine, can be specifically released in the intracellular acid environment, leading to apoptosis of HeLa tumor cells and inhibition of tumor growth. The as-prepared smart drug delivery nanoplatform with persistent luminescence, PLNPs-PAMAM-AS1411/DOX, shows a good application prospect for precise cancer theranostics.

Thiol-yne Click Post-Modification for the Synthesis of Chiral Microporous Organic Networks for Chiral Gas Chromatography.

Microporous organic networks (MONs) have shown great potential in diverse domains recently. However, the application of MONs in chiral separation or catalysis has been largely lagged due to the lack of chiral MONs and the challenge to synthesize chiral MONs. Here we report a facile thiol-yne click strategy to post-synthesize chiral MONs for the first application in chiral gas chromatography. Three chiral MONs with different chiral centers were rationally designed and synthesized to fabricate their capillary columns for gas chromatographic resolution of various chiral compounds with better resolution than three commercial chiral capillary columns. These results show the great potential of the thiol-yne click strategy for constructing newly chiral MONs and their application in chiral separation.

pH-Driven Targeting Nanoprobe with Dual-Responsive Drug Release for Persistent Luminescence Imaging and Chemotherapy of Tumor.

Multifunctional nanoprobes with both imaging and drug delivery capabilities represent an emerging approach to the diagnosis and treatment of tumor. However, poor accumulation in tumor cells and low drug availability are the main limitations for their further application. Here we show a pH-driven targeting nanoprobe with dual-responsive drug release for persistent luminescence imaging and chemotherapy of tumor. The nanoprobe is constructed by conjugating the pH-low-insertion-peptide (pHLIP) to the surface of the core-shell structure of mesoporous silica-coated persistent luminescence nanoparticles (MSPLNPs) with the peptide GFLG and disulfide bond as bridges. The pHLIP functionalized nanoprobe exhibits higher cellular uptake for A549 and HepG2 cells in an acidic extracellular microenvironment (pH < 6.5) than in normal physiological condition (pH 7.4). The nanoprobe possesses well-defined NIR persistent luminescence performance and can be effectively accumulated in the tumor site, leading to the visual HepG2 tumor target imaging without autofluorescence interference. Furthermore, the nanoprobe realizes the dual-responsive release of doxorubicin loaded in the mesoporous channels in systems containing cathepsin B and glutathione, and can effectively kill tumor cells and inhibit the growth of tumor. This integrated nanoprobe possesses great potential for the diagnosis and treatment of tumors with high specificity and efficiency.

Polysiloxane assisted fabrication of chiral crystal sponge coated capillary column for chiral gas chromatographic separation.

Chiral crystalline sponges (CCSs) are a recent class of chiral porous metal complexes potential in chiral recognition. Here we report the fabrication of polysiloxane OV-1701 incorporated CCS-3S (PSO/CCS-3S) coated capillary column as a novel stationary phase for gas chromatographic separation of diverse racemates. CCS-3S with the chiral ligand of (S)-mandelic was selected as the model CCS. With the aid of polysiloxane OV-1701, PSO/CCS-3S coated capillary column gave improved resolution, broader enantiomers separation scope and much larger McReynolds constants than CCS-3S coated capillary column. Many racemates that cannot be separated on CCS-3S coated capillary column were well resolved on PSO/CCS-3S coated capillary column. The PSO/CCS-3S coated capillary column also gave wide linear range, low limit of detection, good repeatability and reproducibility, and fine inertness and anti-column bleeding properties for the separation of enantiomers. In addition, the PSO/CCS-3S coated capillary column presented better resolution for the studied racemates than commercial ß-cyclodextrin based Cyclosil B (30 m long ×0.32 mm i.d. × 0.25 µm film thickness), ß-DEX 225 (30 m long ×0.25 mm i.d. × 0.25 µm film thickness) and amino acid based Chirasil L-Val (25 m long ×0.25 mm i.d. × 0.12 µm film thickness) capillary columns. These results indicate the great potential of PSO/CCS-3S coated capillary column in separation of enantiomers.

In situ fabrication of microporous organic network coated capillary column for high resolution gas chromatographic separation of hydrocarbons.

Microporous organic networks (MONs) are a new class of porous materials synthesized via Sonogashira coupling reactions between organic building blocks. Here we report an in situ synthesis approach to fabricate MONs coated capillary column for high resolution GC separation of hydrocarbons. The McReynolds constant evaluation reveals the MONs coated capillary is a non-polar column. The MONs coated capillary column shows good resolution for GC separation of diverse important industrial hydrocarbons such as linear and branched alkanes, alkylbenzenes, pinene isomers, ethylbenzene and styrene, cyclohexane and benzene. The MONs coated capillary column gave a high column efficiency of 1542 plates per meter for hexane and good precision for replicate separations of the selected hydrocarbons with the RSDs of 0.2-0.3, 1.5-3.1, and 1.9-3.3% for retention time, peak height and peak area, respectively. The MONs coated capillary also offered better resolution than commercial Inert Cap-1 and Inert Cap-5 capillary columns for hexane and heptane isomers. These results reveal the potential of MONs as novel stationary phases in GC.

A multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor cells.

We report the design and fabrication of a multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor. The integration of the dual-stimulus of an acidic microenvironment and laser irradiation with the triple-synergistic therapy of doxorubicin, photothermal and siRNA offers excellent therapeutic performance for drug resistant tumor cells with high specificity and little side effects.

Covalent Organic Frameworks with Chirality Enriched by Biomolecules for Efficient Chiral Separation.

The separation of racemic compounds is important in many fields, such as pharmacology and biology. Taking advantage of the intrinsically strong chiral environment and specific interactions featured by biomolecules, here we contribute a general strategy is developed to enrich chirality into covalent organic frameworks (COFs) by covalently immobilizing a series of biomolecules (amino acids, peptides, enzymes) into achiral COFs. Inheriting the strong chirality and specific interactions from the immobilized biomolecules, the afforded biomolecules⊂COFs serve as versatile and highly efficient chiral stationary phases towards various racemates in both normal and reverse phase of high-performance liquid chromatography (HPLC). The different interactions between enzyme secondary structure and racemates were revealed by surface-enhanced Raman scattering studies, accounting for the observed chiral separation capacity of enzymes⊂COFs.

Biomimetic Persistent Luminescent Nanoplatform for Autofluorescence-Free Metastasis Tracking and Chemophotodynamic Therapy.

Metastasis is the main cause of death in people with cancer. Early diagnosis and targeted therapy for metastasis is crucial for the survival of the cancer patients. However, metastasis is hard to trace for its small size, dispersed distribution and unvascularized anatomy. Here we report a biomimetic persistent luminescent nanoplatform for noninvasive high-sensitive diagnosis and 808 nm laser controlled photodynamics assisted chemotherapy of metastasis. The nanoplatform is composed of a photosensitizer functionalized persistent luminescent nanoparticle core, a doxorubicin loaded hollow silica interlayer and a cancer cell membrane shell for effective metastasis theranostic. The cancer cell membrane shell prevents drug leakage and endows the nanoplatform with targeting ability to metastasis. The reactivatable persistent luminescence of persistent luminescent nanoparticles not only enables long-term in vivo metastasis tracking, but also provides internal light source for singlet oxygen generation to kill cancer cells and further break the membrane shell for drug release. This work provides a promising strategy to develop persistent luminescence imaging guided theranostic nanoplatforms for early metastasis.

A versatile covalent organic framework-based platform for sensing biomolecules.

We herein report the design of a versatile covalent organic framework (COF)-based platform for sensing biomolecules. As a proof of concept, a highly sensitive and selective COF-based fluorescence turn-on detection of DNA and adenosine 5'-triphosphate is demonstrated.

Liposome-Coated Persistent Luminescence Nanoparticles as Luminescence Trackable Drug Carrier for Chemotherapy.

Near-infrared persistent luminescence nanoparticles (NIR-PLNPs) are promising imaging agents due to deep tissue penetration, high signal-to-noise ratio, and repeatedly charging ability. Here, we report liposome-coated NIR-PLNPs (Lipo-PLNPs) as a novel persistent luminescence imaging guided drug carrier for chemotherapy. The Lipo-PLNP nanocomposite shows the advantages of superior persistent luminescence and high drug loading efficiency and enables autofluorescence-free and long-term tracking of drug delivery carriers with remarkable therapeutic effect.

Hydrothermal and biomineralization synthesis of a dual-modal nanoprobe for targeted near-infrared persistent luminescence and magnetic resonance imaging.

The development of the multimodal probes is of great importance for bioimaging application. Herein, we report the fabrication of a functional nanocomposite from near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) and Gd2O3 as a multimodal probe for in vivo NIR persistent luminescence and magnetic resonance (MR) imaging. Small-sized monodispersed NIR ZnGa2O4:Cr3+ PLNPs (ca. 15 nm) were prepared as the NIR persistent luminescence source by a hydrothermal method while hyaluronic acid (HA) functionalized Gd2O3 (HA-Gd2O3) was synthesized as the MR contrast agent via a biomineralization approach. An EDC/NHS coupling strategy was used to connect the amino functionalized PLNPs and the HA-Gd2O3 to give the HA functionalized multimodal probe. The multimodal probe not only exhibits an excellent NIR persistent luminescence signal, but also exhibits larger longitudinal relaxivity (7.38 mM-1 s-1) than commercial contrast agent Gd-DTPA. Moreover, the HA moieties not only enhance the biocompatibility of the multimodal probe, but also endow the probe with tumor-targeting capability. Both in vitro and in vivo bioimaging experiments demonstrate the potential of the multimodal probe for tumor-targeting NIR persistent luminescence and MR imaging.

Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy.

The integrated functions of diagnostics and therapeutics make theranostics great potential for personalized medicine. Stimulus-responsive therapy allows spatial control of therapeutic effect only in the site of interest, and offers promising opportunities for imaging-guided precision therapy. However, the imaging strategies in previous stimulus-responsive therapies are 'always on' or irreversible 'turn on' modality, resulting in poor signal-to-noise ratios or even 'false positive' results. Here we show the design of dual-stimuli-responsive and reversibly activatable nanoprobe for precision tumour-targeting and fluorescence-guided photothermal therapy. We fabricate the nanoprobe from asymmetric cyanine and glycosyl-functionalized gold nanorods (AuNRs) with matrix metalloproteinases (MMPs)-specific peptide as a linker to achieve MMPs/pH synergistic and pH reversible activation. The unique activation and glycosyl targetibility makes the nanoprobe bright only in tumour sites with negligible background, while AuNRs and asymmetric cyanine give synergistic photothermal effect. This work paves the way to designing efficient nanoprobes for precision theranostics.

Activatable Multifunctional Persistent Luminescence Nanoparticle/Copper Sulfide Nanoprobe for in Vivo Luminescence Imaging-Guided Photothermal Therapy.

Multifunctional nanoprobes that provide diagnosis and treatment features have attracted great interest in precision medicine. Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) are optimal materials due to no in situ excitation needed, deep tissue penetration, and high signal-to-noise ratio, while activatable optical probes can further enhance signal-to-noise ratio for the signal turn-on nature. Here, we show the design of an activatable multifunctional PLNP/copper sulfide (CuS)-based nanoprobe for luminescence imaging-guided photothermal therapy in vivo. Matrix metalloproteinases (MMPs)-specific peptide substrate (H2N-GPLGVRGC-SH) was used to connect PLNP and CuS to build a MMP activatable system. The nanoprobe not only possesses ultralow-background for in vivo luminescence imaging due to the absence of autofluorescence and optical activatable nature but also offers effective photothermal therapy from CuS nanoparticles. Further bioconjugation of c(RGDyK) enables the nanoprobe for cancer-targeted luminescence imaging-guided photothermal therapy. The good biocompatibility and the multiple functions of highly sensitive tumor-targeting luminescence imaging and effective photothermal therapy make the nanoprobe promising for theranostic application.

Conjugation of a photosensitizer to near infrared light renewable persistent luminescence nanoparticles for photodynamic therapy.

We report 808 nm NIR light renewable NIR persistent luminescence sensitized photodynamic therapy (PDT). Persistent luminescence provides an internal light source to generate singlet oxygen for PDT. This work paves the way for the next generation of PDT without any need for continuous external light irradiation.

Fabrication and bioconjugation of BIII and CrIII co-doped ZnGa2O4 persistent luminescent nanoparticles for dual-targeted cancer bioimaging.

Persistent luminescent nanoparticles (PLNPs) show great potential in realizing precision imaging due to the absence of in situ excitation and no background interference. However, the current PLNP-based tumour imaging is usually achieved by single targeting or passive targeting strategies, and thus it lacks high specificity and affinity for efficient persistent luminescence imaging in vivo. Herein we report the bioconjugation of multiple targeting ligands on the surface of PLNPs for dual-targeted bioimaging to improve the specificity and affinity of the PLNP nanoprobe for in vitro and in vivo bioimaging. The PLNPs were prepared by co-doping CrIII and BIII into ZnGa2O4via a hydrothermal-calcination method. While CrIII doped ZnGa2O4 PLNPs possess excellent near-infrared luminescence along with long afterglow and red light renewable near-infrared luminescence, doping of BIII into the PLNPs further improves the persistent luminescence. Conjugation of two targeting ligands, hyaluronic acid and folic acid, which have specificity toward the cluster determinant 44 receptor and folic acid receptor in tumour cells, respectively, provides synergistic targeting effects to enhance the specificity and affinity toward tumour cells. This work provides a dual-targeting strategy for fabricating PLNP-based nanoprobes to realize precision tumour-targeted bioimaging.

Penetrating Peptide-Bioconjugated Persistent Nanophosphors for Long-Term Tracking of Adipose-Derived Stem Cells with Superior Signal-to-Noise Ratio.

Reliable long-term in vivo tracking of stem cells is of great importance in stem cell-based therapy and research. Fluorescence imaging with in situ excitation has significant autofluorescence background, which results in poor signal-to-noise ratio (SNR). Here we report TAT penetrating peptide-bioconjugated long persistent luminescence nanoparticles (LPLNP-TAT) for long-term tracking of adipose-derived stem cells (ASC) without constant external excitation. LPLNP-TAT exhibits near-infrared emitting, red light renewable capability, and superior in vivo imaging depth and SNR compared with conventional organic dye and quantum dots. Our findings show that LPLNP-TAT can successfully label ASC without impairing their proliferation and differentiation and can effectively track ASC in skin-regeneration and tumor-homing models. We believe that LPLNP-TAT represents a new generation of cell tracking probes and will have broad application in diagnosis and therapy.

Radiopaque tantalum oxide coated persistent luminescent nanoparticles as multimodal probes for in vivo near-infrared luminescence and computed tomography bioimaging.

The design and fabrication of multimodal imaging nanoparticles is of great importance in medical diagnosis. Here we report the fabrication of core-shell structured Zn2.94Ga1.96Ge2O10:Cr(3+),Pr(3+)@TaOx@SiO2 nanoparticles for persistent luminescence and X-ray computed tomography (CT) imaging. Persistent luminescent nanoparticles Zn2.94Ga1.96Ge2O10:Cr(3+),Pr(3+) were used as the core to provide near-infrared luminescence, and a TaOx layer was grown on the core to serve as the contrast agent for CT. The tenuous outermost SiO2 shell was fabricated on the TaOx layer to gain high biocompatibility and to facilitate post-modification with tumor-targeting peptides. The fabricated core-shell structured nanoparticle shows intense near-infrared luminescence and the CT contrast effect. No obvious mutual interference was found in these two modalities, which ensures that each imaging modality merits could be brought in a full play. Furthermore, covalent bonding of cyclic-Asn-Gly-Arg peptides makes the core-shell structured nanoparticles promising for in vivo targeted imaging of tumor-bearing mice.