Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

The effects of health risk behaviors to excess mortality in the population with depression: A cohort study based on NHANES data.

BACKGROUND: The population with depression had a considerable excess mortality risk. This increased mortality may be attributed to the biological consequences of depression or the substantial prevalence of health risk behaviors (HRBs). This study aimed to quantify the combined effects of four major HRBs - smoking, excessive alcohol use, physical inactivity, and an unhealthy diet - on excess mortality among depressed individuals. METHODS: This study included 35,738 adults from the National Health and Nutrition Examination Survey 2005-06 to 2017-18, with mortality follow-up data censored through 2019. The standardized prevalence of HRBs was calculated for populations with and without depression. Poisson regression models were used to calculate the mortality rate ratio (MRR). Based on model adjusting for socio-demographic factors, the attenuation of MRR was determined after further adjustment for HRBs. RESULTS: A total of 3147 participants were identified as having depression. All HRBs showed a significantly higher prevalence among the population with depression. After adjusting for socio-demographic factors, depression was associated with 1.7 and 1.8 times higher all-cause and cardiovascular disease mortality rate, respectively. Further adjustment for all current HRBs resulted in a 21.9 % reduction in all-cause mortality rate and a 15.4 % decrease in cardiovascular disease mortality rate. LIMITATION: HRBs were reported at a single time point, and we are unable to demonstrate a causal effect. CONCLUSION: At least 1/5 of excess mortality for population with depression was attributable to HRBs. Efforts should be made to address HRBs among population with depression.

Pure Covalent-Organic Framework Membrane as a Label-Free Biomimetic Nanochannel for Sensitive and Selective Sensing of Chiral Flavor Substances.

Chiral flavor substances play an important role in the human perception of different tastes. Here, we report a pure covalent-organic framework (COF) membrane nanochannel in combination with a chiral gold nanoparticles (AuNPs) selector for sensing chiral flavor substances. The pure COF membrane with a proper pore size is selected as the nanochannel, while l-cysteine-modified AuNPs (l-Cys-AuNPs) are used as the chiral selector. l-Cys-AuNPs show stronger binding to the S-enantiomer than the R-enantiomer, causing current reduction to different degrees for the R- and S-enantiomer to achieve chiral sensing due to the synergistic effect of the size exclusion of the COF nanochannel and the chiral selectivity of l-Cys-AuNPs. The developed COF membrane nanochannel sensing platform not only allows an easy balance of the permeability and selectivity, which is difficult to achieve in traditional polymer membrane nanochannel sensors, but also exhibits better chiral performance than commercial artificial anodic aluminum oxide (AAO) nanochannel sensors. The developed nanochannel sensor is successfully applied for sensing flavor enantiomers such as limonene, propanediol, methylbutyric acid, and butanol with the enantiomer excess values of 55.2% (propanediol) and 72.4% (limonene) and the low detection limits of 36 (limonene) and 71 (propanediol) ng L-1. This study provides a new idea for the construction of nanochannel platforms based on the COF for sensitive and selective chiral sensing.

The combined association of adherence to recommended physical activity and glycemic control with depression: an exploratory study with mediation and moderation models.

BACKGROUND: Both physical activity and dysglycemia are associated with depression. However, the combined association of adherence to recommended physical activity (RPA) and glycemic control with depression is unknown. Moreover, the extent to which glycemic control mediates the association between physical activity and depression is not established. METHODS: The sample included 31,302 adults from the National Health and Nutrition Examination Survey 2007-08 to 2017-18. Adherence to RPA for aerobic activity was defined according to the WHO 2020 guidelines. HbA1c was classified as < 5.7%, 5.7-6.4%, 6.5-6.9%, and ≥ 7.0%. Depression was evaluated according to the 9-item Patient Health Questionnaire. The odds ratio for depression stratified by adherence to RPA and HbA1c level were estimated by logistic regressions. Mediation analysis was performed to estimate the direct associations (not through glycemic control) and indirect associations (through glycemic control). RESULTS: A total of 2871 participants were diagnosed with depression. Compared to participants with HbA1c level < 5.7% who adhere to RPA, those with HbA1c level < 5.7%, 5.7-6.4%, 6.5-6.9%, and ≥ 7.0% who did not adhere to RPA had increased odds ratio for depression, especially in women and older adults. Individuals with HbA1c ≥ 7.0% still had an increased odds ratio for depression even though they were physically active. The results of the mediation analysis were insignificant. CONCLUSION: There was a combined association of adherence to RPA and glycemic control with depression in women and older adults. We did not find out evidence of glycemic control mediation on the pathway from physical activity to depression.

General Two-Step Method for the Fabrication of Covalent-Organic Framework-Bound Open-Tubular Capillary Columns for High-Resolution Gas Chromatography Separation of Isomers.

Covalent organic frameworks (COFs) are promising as stationary phases for gas chromatography (GC). The successful anchoring of COFs to the inner walls of the capillary with good uniformity is an important prerequisite to ensure the excellent separation performance of columns. However, current methods for the fabrication of COF-based capillary columns cannot always meet this requirement when faced with different COFs, which hampers the further development of COF-based GC stationary phases. Here, we show a general two-step method for the fabrication of COF-bound capillary column. The first step enables the formation of uniform amorphous polymer layer on the inner walls of capillary, while the second step allows the facile transformation of the amorphous polymer layer into a highly crystalline COF layer. COF-bound capillary columns with different framework structures were fabricated successfully by the developed two-step method. Impressively, the COF layers bound on the inner walls of these capillary columns showed good uniformity and high crystallinity. More importantly, as an example, the fabricated Tab-DHTA-bound capillary column showed good resolution (R > 1.5) and high column efficiency (700-39,663 plates m-1) for the tested isomers of ethylbenzene, xylene, dichlorobenzene, chlorotoluene, pinene, 1,3-dichloropropene, and propylbenzene with good precision (RSD, run-to-run, n = 5) (retention time, 0.2-0.6%; peak area, 0.5-1.1%; and peak height, 0.5-1.4%). In general, the fabricated Tab-DHTA-bound capillary column exhibited better performance for the separation isomers than commercial columns DB-5 and HP-FFAP. These results indicate that the two-step method is an efficient way to fabricate the COF-bound capillary column with excellent separation performance.

Particle Size Regulation of Single-Crystalline Covalent Organic Frameworks for High Performance of Gas Chromatography.

Although polycrystalline covalent organic frameworks (PCOFs) have already shown great potential as stationary phases for chromatography, irregular shape and size distribution of PCOFs make regulation of particle size of PCOFs for high separation performance impossible, which is accessible by the application of single-crystalline COFs (SCOFs). Herein, we showed preparation of three-dimensional SCOF (SCOF-303) bonded capillaries (SCOF-303-capillary) with different particle sizes (about 0.4-1.6 µm) and further investigated gas chromatographic separation ability of these SCOF-303-capillaries for isomers of xylene, dichlorobenzene, and pinene. It was found resolution and column efficiency of SCOF-303-capillaries for isomers decreased with the increase in particle size, mainly resulting from the weaker size-exclusion effect and higher mass transfer resistance of the larger particle size of flexible SCOF-303. The obtained SCOF-303-capillary (particle size of ∼0.4 µm) offered baseline separation of xylene isomers with the high resolution of 2.26-3.52, great efficiency of 7879 plates m-1 for p-xylene, better than PCOF-303-capillary, and commercial DB-5 and HP-FFAP capillary columns as well as many reported capillaries. This work not only shows the great potential of SCOFs for gas chromatography but also provides the theoretical direction for the design of the efficient COF based stationary phase by adjusting the particle sizes.

Reductive dechlorination of chlorinated ethenes by ball milled and mechanochemically sulfidated microscale zero valent iron: A comparative study.

Ball milling is an effective technique to not only activate and reduce the size of commercial microscale zero valent iron (mZVI) but also to mechanochemically sulfidate mZVI. Yet, little is known about the difference between how chlorinated ethenes (CEs) interact with ball milled mZVI (mZVIbm) and mechanochemically sulfidated mZVI (S-mZVIbm). We show that simple ball milling exposed the active Fe0 sites, while mechanochemical sulfidation diminished Fe0 sites and meanwhile increased S2- sites. Mechanochemical sulfidation with [S/Fe]dosed increased from 0 to 0.20 promoted the particle reactivity most for TCE dechlorination (∼14-fold), followed by PCE and 1,1-DCE while it diminished the reactivity for trans-DCE (∼0.4-fold), cis-DCE (∼0.02-fold) and VC (∼0.002-fold) compared to simple ball milling. Sulfidation also improved the electron efficiency of CE dechlorination, except for cis-DCE and VC. The kSA of cis-DCE, VC and trans-DCE dechlorination positively correlated with surface Fe0 content, suggesting their dechlorination was mainly mediated by Fe0 site or reactive atomic hydrogen. The kSA of TCE dechlorination positively correlated with surface S2- content and the dechlorination mainly occurred on S2- sites via direct electron transfer. Increased sulfidation favored direct electron transfer mechanism. The kSA of PCE and 1,1-DCE was not dependent on either parameter and their dechlorination was equally achieved through either mechanism.

Building-block exchange synthesis of amino-based three-dimensional covalent organic frameworks for gas chromatographic separation of isomers.

Thermally stable three-dimensional covalent organic frameworks (3D COFs) with rich pores of channels and cages are promising as stationary phases for gas chromatography (GC), which has not been explored. Here we synthesize the first amino-based 3D COF and its covalently bonded capillary via building-block exchange for GC separation of isomers.

Hydroxyl-functionalized three-dimensional covalent organic framework for selective and rapid extraction of organophosphorus pesticides.

The wide utilization of organophosphorus pesticides (OPPs) results in a potential threat to ecosystem and human health. The essential extraction process in practical OPPs analysis always suffers from the low efficiency due to the limited accessible active sites and interactions in the adsorbents. Here, we report a rational design and synthesis of a novel hydroxyl-functionalized three-dimensional covalent organic framework (3D COF-OH) named JNU-6 with ordered porous structure and multiple interactions as the adsorbent for rapid and selective dispersive solid phase extraction (DSPE) of OPPs. The 3D COF-OH based DSPE was coupled with gas chromatography-flame thermionic detection (GC-FTD) for the determination of four selected OPPs with low limits of detection of 0.15-0.39 ng mL-1, wide linear range of 1-1100 ng mL-1. The developed method gave good precision (relative standard deviation of 1.6-8.5% (n = 5)) and recoveries of 86-106% for the determination of OPPs in complicated fruit and vegetable samples. This work reveals the high practical potential of functionalized 3D COFs as adsorbents for effective extraction of trace contaminants in complicated samples.

Post-modification of covalent organic framework for gas chromatographic separation of isomers.

Separation of isomers is important in diverse areas such as life science, chemical industry, pharmaceutical and environmental science, but still challenging due to their similar physicochemical properties. Development of new stationary phases is an effective way to improve the performance of chromatography for the separation of isomers. Here, we report the post-modification of a new hydroxyl-functionalized covalent organic framework (COF) TzDHNDA with [(1-phenylethyl)amino]acetic acid (PEAA) via esterification reaction to construct PEAA functionalized COF (TzDHNDA-PEAA). The prepared TzDHNDA-PEAA was stable up to 380 °C and used as stationary phase to make TzDHNDA-PEAA coated capillary column for gas chromatographic separation of isomers. The TzDHNDA-PEAA coated capillary column showed a high column efficiency for n-dodecane (12417 plates m-1, 120 °C) and high resolution separation of the isomers of fluoroaniline (Rm-/o-=3.2, Rp-/m-=2.4), chloroaniline (Rm-/o-=5.7, Rp-/m-=1.8), nitrotoluene (Rp-/o-=2.2, Rm-/p-=1.7), pinene (Rß-/α-=2.4), ionone (Rß-/α-=4.8) and 1,3-dichloropropene (RE-/Z-=2.0). The fabricated column offered better separation of chloroaniline isomers than commercial capillary columns InertCap WAX, InertCap 1701 and InertCap 5. The introduced benzene ring, secondary amine and carbonyl groups of PEAA into the COF TzDHNDA significantly improved the resolution of isomers due to the enhanced hydrogen-bonding and π-π interactions. This work shows that post-modification strategy is an effective way to prepare novel COFs for chromatographic separation of isomers.

Bacterial microenvironment-responsive dual-channel smart imaging-guided on-demand self-regulated photodynamic/chemodynamic synergistic sterilization and wound healing.

Bacterial infections pose a serious threat to public health. The integration of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has emerged as a promising means to combat bacterial infection. However, most photosensitizers are often in the "always on" activated state and lack bacterial targeting, leading to non-specific damage to normal tissues. Besides, most of the conventional CDT systems are directly complexed with metal ions. The toxicity of excess free metal ions cannot be ignored. Therefore, it is a huge challenge to construct a bacteria-specific activated PDT/CDT synergistic therapy platform to achieve precise sterilization. Herein, we report a bacterial microenvironment-responsive phosphorescence/fluorescence dual-channel smart imaging-guided on-demand self-regulating CDT/PDT theranostic platform for precise sterilization and wound healing. Acid-degradable persistent luminescence nanoparticles were prepared as bacterial microenvironment-responsive phosphorescence imaging units and CDT agents. Piperazine-modified PEG was then introduced as an intelligent targeting and hydrophilic group, which was further bonded with a pH-reversibly-activated fluorescence/PDT-in-one probe to construct the intelligent theranostic platform. The developed platform combines the features of good biocompatibility, prolonged blood circulation, charge-reversed intelligent targetability, dual-channel smart imaging and on-demand self-regulating CDT/PDT effect, holding great potential for precise imaging-guided bacteria-specific synergistic sterilization without side effects.

Ratiometric Luminescence Aptasensor Based on Dual-Emissive Persistent Luminescent Nanoparticles for Autofluorescence- and Exogenous Interference-Free Determination of Trace Aflatoxin B1 in Food Samples.

Sensitive and accurate determination of aflatoxin B1 (AFB1) is of great significance to food safety and human health as it is recognized as the most toxic mycotoxin and carcinogenic. Herein, we report a ratiometric luminescence aptasensor based on dual-emissive persistent luminescent nanoparticles (PLNP) for the accurate determination of trace AFB1 in complex food samples without autofluorescence and exogenous interference. Dual-emissive PLNP ZnGa2O4:Cr0.0001 was prepared first and acted as the donor for energy transfer as well as the signal unit with phosphorescence at 714 and 508 nm (the detection and the reference signal, respectively). AFB1 aptamer was then bonded on the surface of PLNP to offer specific recognition ability. Aptamer complementary DNA modified with Cy5.5 was employed as the acceptor for energy transfer and the quenching group to eventually develop a turn-on ratiometric luminescence aptasensor. The developed ratiometric luminescence aptasensor combined the merits of long-lasting luminescence, in situ excitation and autofluorescence-free of PLNP, exogenous interference-free and self-calibration reading of ratiometric sensor, as well as the high selectivity of aptamer, holding great promise for accurate determination of trace AFB1 in complex matrix. The developed ratiometric aptasensor exhibited excellent linearity (0.05-70 ng mL-1), low limit of detection (0.016 ng mL-1), and good precision (2.3% relative standard deviation for 11 replicate determination of 1 ng mL-1 AFB1). The proposed ratiometric aptasensor was successfully applied for the determination of AFB1 in corn, wheat, peanut, millet, oats, and wheat kernels with recoveries of 95.1-106.5%.

Size- and shape-dependent cytotoxicity of nano-sized Zr-based porphyrinic metal-organic frameworks to macrophages.

The wide utilization of nano-sized metal-organic frameworks (NMOFs) leads to inevitable health risks to humans. Previous studies on health risks of NMOFs mainly focus on the cytotoxic tests of typical NMOFs，but lack sufficient studies on the effects of physiochemical characteristics of NMOFs on the cytotoxicity and the related mechanisms. Here, four kinds of Zr-based porphyrinic NMOFs (PCNs), including spherical 30, 90, and 180 nm PCN-224 and rod-like 90 nm PCN-222, were taken as a proof of the concept to investigate the effects of the size and shape of NMOFs on the cytotoxicity and related mechanisms to macrophages. The 30 nm spherical PCN-224 induced significant rupture of cell membrane and dissolved in lysosome, leading to the most significant cell necrosis among the studied other nano-sized PCNs. However, other studied PCNs showed insignificant membrane rupture and their dissolution in lysosome. Furthermore, the 90 nm-sized PCN-224 led to much more significant cell necrosis by inducing lysosome damage and inhibiting of autophagy flux than the rod-like 90 nm PCN-222. These findings reveal the size- and shape-dependent cytotoxicity of PCNs and the related mechanisms and are helpful to the assessment of the potential health risks of NMOFs and the safe application of NMOFs.

Responsive nanoplatform for persistent luminescence "turn-on" imaging and "on-demand" synergistic therapy of bacterial infection.

Multifunctional nanotheranostic platforms are emerging for the treatment of bacterial infections. Uncontrollable drug release and poor response in target location leads to inefficient therapy and failure to offer timely antibacterial monitoring. Here, we report a multifunctional nanoplatform that can be triggered by the bacterial microenvironment for effective bacterial killing and high-sensitive persistent luminescence (PL) "turn-on" imaging. Hyaluronic acid (HA) is grafted on the surface of mesoporous silica-coated persistent luminescence nanoparticles (PLNPs@MSN) loaded with cinnamaldehyde (CA). Further in situ growth of MnO2 shells gives PLNPs@MSN@CA-HA-MnO2 (PMC-HA-MnO2). MnO2 shell of PMC-HA-MnO2 can be reduced to Mn2+ by the H2O2 in the bacterial microenvironment to trigger persistent luminescence (PL) "turn-on" imaging along with chemodynamic therapy (CDT). Meanwhile, HA can response to bacterially secreted hyaluronidase to make the packaged CA release controllable and "on-demand". Consequently, PMC-HA-MnO2 enables effective response to bacterial-infected region, ensuring high-sensitive "turn-on" imaging, synergistic CDT, accurate targeting and "on-demand" CA release to give great antibacterial effect. This nanoplatform has great potential for the diagnosis and treatment of multidrug-resistant bacterial infection with high specificity and efficiency.

One-step integrated sample pretreatment technique by gas-liquid microextraction (GLME) to determine multi-class pesticide residues in plant-derived foods.

Gas-liquid microextraction technique (GLME) has been integrated with dispersive solid phase extraction to establish a one-step sample pretreatment approach for rapid analysis of multi-class pesticides in different plant-derived foods. A 50 µL of organic solvent plus 40 mg of PSA were required throughout the 5-minute pretreatment procedure. Good trueness (recoveries of 67.2 - 105.4%) and precision (RSD ≤ 18.9%) were demonstrated by the one-step GLME method, with MLOQs ranged from 0.001 to 0.011 mg kg-1. As high as 93.6% pesticides experienced low matrix effect through this method, and the overall matrix effects (ME%) were generally better or comparable to QuEChERS. This method successfully quantified 2-phenylphenol, quintozene, bifenthrin and permethrin in the range of 0.001 - 0.008 mg kg-1 in real food samples. The multiresidue analysis feature of GLME has been validated, which displays further potential for on-site determination of organic pollutants in order to safeguard food safety and human health.

A unique self-reporting photosensitizer enabling simultaneous photodynamic therapy and real-time monitoring of phototheranostic process in a dynamic dual-color mode.

Phototheranostics has attracted great interest in cancer therapy. Small-molecule self-reporting photosensitizers, one kind of idea agent in phototheranostics, enables simultaneous photodynamic therapy (PDT) and feedback of therapeutic efficacy. However, previous such photosensitizers exclusively employed the change of single emission to monitor cell death, which can be disturbed by variations in photosensitizer concentration and the excitation intensity. Herein, we report a unique self-reporting photosensitizer TPA-3PyA+ constructed from a twisted triphenylamine unit (TPA), three benzene ring units and three cyanovinyl-pyridinium units (PyA) for PDT and its real-time monitoring in a dynamic dual-color mode. TPA-3PyA+ possesses a rotatable electron donor-π bridge-electron acceptor framework and exhibits high singlet oxygen quantum yield (124%) and a twisted intramolecular charge transfer (TICT) effect. TPA-3PyA+ not only enables effective staining of cancer cells with dual-color fluorescence due to the TICT effect but also shows excellent PDT performance. The simultaneous change in emission color, intensity and intracellular location of TPA-3PyA+ during cell death allows it to self-report cell death. Moreover, the change of dual-emission color allows distinguishing living and dead cells and effectively avoids interference in previous single-emission self-reporting photosensitizers. This work highlights the great potential of a self-reporting photosensitizer with dual-color emissions for efficient feedback of theranostics.

Nanothorn Filter-Facilitated Online Cell Lysis for Rapid and Deep Intracellular Profiling by Single-Cell Mass Spectrometry.

Mass spectrometry combined with flow cytometry is emerging for high-throughput single-cell metabolite analysis but still has problems with limited intracellular information coverage. Here, we show a simple and efficient all-in-one system integrating cell injection, cell extraction, online cell lysis, analyte ionization, and mass spectrometric detection for rapid single-HeLa-cell screening with in-depth profiling of cellular metabolites and drugs. Zinc oxide nanothorn-decorated filters with three bore sizes (5.22, 8.36, and 16.75 µm) were fabricated for efficient online lysis of the cell membrane (even nuclear membrane) to facilitate intracellular analyte release and demonstrated to have a size effect for potential subcellular discrimination. The two smaller-bore filters gave 2-11-fold improvements in signal response for representative intracellular metabolites, such as adenosine, glutamine, and leucine/isoleucine. Especially, the smallest-bore filter enabled successful detection of the metabolites in the nucleus, including tetrahydrobiopterin and cyclic guanosine monophosphate. The developed all-in-one system was explored to monitor the uptake of four anticancer drugs, including 5-fluorouracil, doxorubicin, gambogic acid, and paclitaxel in single cells, and further to investigate the drug uptake trends at the subcellular level. The all-in-one system integrates the merits of high-throughput single-cell screening and in-depth intracellular information profiling and is promising for high-coverage single-cell metabolome analysis to serve cell biology research and cancer research.

Fabrication of G-quadruplex/porphyrin conjugated gold/persistent luminescence theranostic nanoprobe for imaging-guided photodynamic therapy.

Photodynamic therapy (PDT) received great attention in cancer therapy due to the advantages of negligible drug resistance, low side effects, and minimal invasiveness. Development of theranostic nanoprobes with specific imaging-guided PDT is of great significance in the field. Herein we report the fabrication of a novel theranostic nanoprobe porphyrin/G-quadruplex conjugated gold/persistent luminescence nanocomposites for imaging-guided PDT. The developed nanoprobe contains NIR-emitting persistent luminescent nanoparticles (PLNP) as the core for autofluorescence-free bioimaging and Au coating on PLNP for facile subsequent DNA conjugation. The DNA sequence is designed to contain G-rich AS1411 aptamer for recognizing the over-expressed cellular nucleolin of cancer cell and forming a G-quadruplex structure to combine with tetrakis (4-carboxyphenyl) porphyrin (TCPP) to realize PDT. The AS1411 aptamer-contained DNA conjugated Au-coated PLNP is rapidly prepared via a freezing method with high content of DNA and good aqueous stability. Meanwhile, TCPP is easily loaded into the G-quadruplex structure formed from G-rich AS1411 aptamer on the surface of Au/PLNP in presence of K+. The theranostic nanoprobe gives integrated merits of PLNP for autofluorescence-free bioimging, TCPP for PDT and AS1411 aptamer-contained DNA for specific binding to cancer cells. This work provides a new specially designed imaging-guided PDT nanoplatform for theranostics.

Neutrophil Delivered Hollow Titania Covered Persistent Luminescent Nanosensitizer for Ultrosound Augmented Chemo/Immuno Glioblastoma Therapy.

Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood-brain-barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil-delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa2 O4 :Cr3+ (ZGO) core for persistent luminescence imaging and a hollow sono-sensitive TiO2 shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti-PD-1 antibody) is trapped in the interior of the porous ZGO@TiO2 with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO2 @ALP. Delivered by neutrophils (NEs), ZGO@TiO2 @ALP-NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO2 @ALP, leading to liposome destruction for PTX and anti-PD-1 antibody release to kill tumors and induce local inflammation, which in-turn attractes more ZGO@TiO2 @ALP-NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long-term immuno-surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers.

Dual-Emissive Persistent Luminescence Nanoparticle-Based Charge-Reversible Intelligent Nanoprobe for Persistent Luminescence-Ratio Bioimaging along with Chemo-Photothermal Synergic Therapy.

Persistent luminescence nanoparticles (PLNPs) hold great promise for bioimaging owing to no demand for in situ excitation and negligible tissue autofluorescence interference. Nevertheless, huge challenges remain in the further development of single-emissive PLNPs due to the great variation of luminescence with time after excitation ceases. Herein, we report the controllable fabrication of dual-emissive monodispersed PLNPs (ZnGa2O4:Cr) by a surfactant-assisted hydrothermal method in combination with postcalcination for bioimaging. The prepared PLNPs emit luminescence at 508 and 714 nm with a constant luminescence ratio (I508/I714) for more than 1 h after UV excitation stops. Moreover, the prepared PLNPs give a constant I508/I714 ratio signal after repeated excitation by a LED lamp, allowing luminescence ratio imaging to ensure the long-term accuracy for in vivo imaging. In vivo ratio imaging demonstrates the potential of the prepared PLNPs for precision bioimaging. In addition, the prepared PLNPs have been applied to fabricate a theranostic nanoprobe with intelligent tumor-targeted imaging and chemo-photothermal synergistic therapy to further reveal their unique advantage for imaging guided therapy. We believe that the dual-emissive PLNPs will provide a promising nanoplatform for bioimaging and biomedical applications.