NIR-Triggered On-Demand Nitric Oxide Release for Enhanced Synergistic Phototherapy of Hypoxic Tumor.

Hypoxia of tumor microenvironments is a major factor restricting tumor treatment, which causes progression and metastasis of tumor. The hypoxic tumor microenvironment not only makes the traditional treatment method, such as chemotherapy, ineffective but also hinders the O2-dependent treatments, such as photodynamic therapy (PDT). Recently, stimuli-responsive nitric oxide (NO) donors have attracted extensive research interest in hypoxic tumor treatment because the NO release process is O2-independent. Besides, NO can distribute more uniformly than drug molecules and more widely than the PDT-generated active species due to its strong diffusion ability (200 µm in cells) and long lifetime (2 s in cells). Encouraged by these advantages, a near infrared light-triggered NO release polymeric nanoplatform (P1-CapNO NPs) was constructed by a thermally sensitive NO release unit, a photothermal unit, and a hydrophilic polyethylene glycol unit. P1-CapNO NPs possess strong absorption in the NIR region (the wavelength of maximal absorption peak was 790 nm with a molar absorption coefficient of 2.4 × 105 M-1 cm-1), great photothermal conversion efficiency (23.8%), and NO release ability (the released NO concentration can reach 1.3 µM) under 808 nm laser irradiation. Owing to these advantages, the great synergistic antitumor effect can be achieved in vitro and in vivo even under the hypoxic environment. The synergistic therapeutic strategy in this work could bypass the obstacles caused by hypoxia in tumor treatment and provide a reference for building a NO-involved therapeutic platform.

Dynamics of heavy metals during the development and decomposition of leaves of Avicennia marina and Kandelia obovata in a subtropical mangrove swamp.

In mangrove wetlands, leaves make up a high proportion of the plant biomass and can accumulate heavy metals from contaminated sediment. Despite this, it is still unclear how heavy metal concentrations in leaves change as they develop and how metals in senescence leaves are recycled back into the mangrove ecosystems during decomposition. The present study aims to investigate the dynamics of six heavy metals (Cu, Zn, Cr, Ni, Cd, and Pb) in leaves of two common mangrove plants, Avicennia marina and Kandelia obovata, at different stages of development (young, mature, and senescent) and leaf litter decomposition (from 0 to 20 weeks). Based on litterbag experiments in a subtropical mangrove swamp, both plant species showed similar trends in alternations of the six heavy metals during leaf development, that was, decreased in Cu and Zn but increased in Pb, while Cr, Ni, and Cd remained steady. All heavy metals in litter gradually increased in concentration during decomposition. By the end of the 20-weeks decomposition, the concentrations of Cu, Zn, and Cd in decayed leaves were comparable to those in sediment, with Cu, Zn, and Cd at approximately 18, 75, and 0.2 mg·kg-1, respectively, while Cr (66 mg·kg-1), Ni (65 mg·kg-1), and Pb (55 mg·kg-1) were lower than those in sediment, indicating that metals were not retained in litter but recycled back to the sediment. Tannins in mangrove leaf litter might chelate heavy metals, affecting their migration and transformation of heavy metals in estuarine mangrove wetlands. The findings of our study provide insight into the interactions between toxic heavy metals and mangrove plant species during leaf development, representing the first example of how most metals would be retained in leaf litter during decomposition, thereby reducing their release to estuarine and marine ecosystems.

Time-Resolved Luminescent Sensing and Imaging for Enzyme Catalytic Activity Based on Responsive Probes.

Enzymes, as a kind of biomacromolecules, play an important role in many physiological processes and relate directly to various diseases. Developing an efficient detection method for enzyme activity is important to achieve early diagnosis of enzyme-relevant diseases and high throughput screening of potential enzyme-relevant drugs. Time-resolved luminescence assay provide a high accuracy and signal-to-noise ratios detection methods for enzyme activity, which has been widely used in high throughput screening of enzyme-relevant drugs and diagnosis of enzyme-relevant diseases. Inspired by these advantages, various responsive probes based on metal complexes and metal-free organic compounds have been developed for time-resolved bioimaging and biosensing of enzyme activity owing to their long luminescence lifetimes, high quantum yields and photostability. In this review, we comprehensively reviewed metal complex- and metal-free organic compound-based responsive probes applied to detect enzyme activity through time-resolved imaging, including their design strategies and sensing principles. Current challenges and future prospects in this rapidly growing field are also discussed.

Microcosm study on cold adaptation and recovery of an exotic mangrove plant, Laguncularia racemosa in China.

Laguncularia racemosa (a white mangrove) is an exotic mangrove species commonly distributed in southern intertidal zones in China since it was introduced for reforestation purposes in 1999. However, the invasiveness of this exotic species and its cold adaptability have rarely been reported. The present work determined the cold resistance level of L. racemosa and its recovery from cold stress, aiming to speculate its potential invasive capability in China. Results showed that the germination of L. racemosa seeds in sand or in simulated sea field models was significantly inhibited by a series of cold treatments, with no germination at 5 °C and decreased in germination at low temperatures (15-25 °C). Low temperature also reduced net photosynthetic rate (A), water use efficiency (WUE), transpiration rate (E), and stomatal conductance (Gs) of the seedlings of L. racemosa. On the other hand, cold stress up-regulated in leaves of malondialdehyde (MDA) and antioxidant activities, including superoxide dismutase (SOD), glutathione reductase (GR), and ascorbate peroxidase (APX). Additionally, these physiological and biochemical indexes of cold-stressed L. racemosa could recover to the original levels if the plants were returned to room temperature with a few exceptions. For instance, the cold exposure duration altered seedlings' physiology, but the photosynthetic related activities could not recover if cold treatment lasted for 120 h. This study suggests that L. racemosa can tolerate low temperatures to some extent, thus settle and even invade the coast of China at high latitudes having cold winter, which poses a challenge to the conservation and management of local mangrove ecosystems.

Overcoming Tumor Hypoxia through Multiple Pathways Using an All-in-One Polymeric Therapeutic Agent to Enhance Synergistic Cancer Photo/Chemotherapy Effects.

Hypoxia is a significant characteristic of tumors, which causes aggressive tumor growth and strong therapy resistance. Inspired by the improved therapeutic efficacy of synergistic treatment, herein, an all-in-one polymeric therapeutic agent was developed, which could overcome tumor hypoxia through multiple pathways. Multiple therapeutic agents were incorporated into the polymer, including the singlet oxygen (1O2) carrier unit to store cytotoxic reactive oxygen species, the photosensitized and photothermal unit to trigger the capture and release of 1O2, and the hypoxia-responsive prodrug unit to maintain a long-term tumor inhibition. In addition, the hydrophilic polyethylene glycol unit was also introduced to improve water-solubility and biocompatibility. Importantly, this study achieved the capture and controllable release of 1O2 just by regulating the power of an 808 nm laser for the first time, which is more convenient and flexible than previous works. As expected, the as-prepared copolymer displayed reduced oxygen dependence, accompanied with promising synergistic anti-tumor and anti-recurrence efficacies under hypoxic in vitro and in vivo environments. Consequently, this synergistic anti-hypoxia strategy may open up new avenues in the design of all-in-one therapeutic platforms for promoting the development of accurate, efficient, and long-acting treatment in clinical studies.

Rational Design of Near-Infrared-Absorbing Pt(II)-Chelated Azadipyrromethene Dyes as a New Generation of Photosensitizers for Synergistic Phototherapy.

Pt(II) photosensitizers are emerging as novel Pt anticancer agents for cancer photodynamic therapy (PDT) to avoid uncontrollable toxicity of cisplatin. However, the application of Pt(II) photosensitizers is limited by tumor hypoxia and the poor penetration depth of excitation light. To overcome these drawbacks, exploiting the next generation of Pt anticancer agents is of urgent need. According to theoretical calculations, novel near-infrared (NIR)-absorbing Pt(II)-chelated azadipyrromethene dyes (PtDP-X, where X = N, C, and S) were designed. Importantly, spin-orbit coupling of the Pt atom could promote the intersystem crossing of a singlet-to-triplet transition for converting oxygen to singlet oxygen (1O2), and the azadipyrromethene skeleton could provide a strong photothermal effect. As expected, PtDP-X exhibited intense NIR absorption and synergistic PDT and photothermal effects with low dark cytotoxicity. Furthermore, water-soluble and biocompatible PtDP-N nanoparticles (PtDP-N NPs) were prepared that achieved effective tumor cell elimination with low side effects under 730 nm light irradiation in vitro and in vivo. This pioneering work could push the exploitation of NIR-absorbing metal-chelated azadipyrromethene dyes, so as to promote the positive evolution of phototherapy agents.

A photothermally-induced HClO-releasing nanoplatform for imaging-guided tumor ablation and bacterial prevention.

Photothermal therapy (PTT) is a cure that can inhibit tumor growth effectively and even remove tumor via photo-induced local hyperthermia. However, its shortcoming lies in the fact that excessive heat is most likely to lead to thermal injury at the epidermis of the tumor region and even the area of the surrounding tissue. As a consequence, the exposure of the thermally-induced wound would result in the increased risk of bacterial infection. To date, few PTT platforms have attached importance to the prevention of bacterial infection at the photothermally-induced wound. Herein, we reported a thermally-sensitive liposome nanosystem (Lipo-B-TCCA) containing aza-BODIPY and trichloroisocyanuric acid, which is conductive for the PTT of tumor and the prevention of bacteria. It is observed that the designed nanoplatform could exhibit remarkable stability, high photothermal conversion efficiency (31.4%), and efficient HClO-releasing ability in vitro and in vivo. Moreover, Lipo-B-TCCA is able to eliminate tumor efficiently via near infrared fluorescence and photothermal imaging guidance with low side effects. Most importantly, Lipo-B-TCCA could prevent the growth of S. aureus in the thermal wound during the process of PTT. The imaging-guided photothermally-induced HClO-releasing PTT nanoplatform for tumor ablation and bacterial prevention shows excellent performance and great potential for biomedical applications.

Rational Design of Efficient Organic Phototherapeutic Agents via Perturbation Theory for Enhancing Anticancer Therapeutics.

The development of efficient phototherapeutic agents (PTA) through rational and specific principles exhibits great potential to the biomedical field. In this study, a facile and rational strategy was used to design PTA through perturbation theory. According to the theory, both the intersystem crossing rate for singlet oxygen generation and nonradiative transition for photothermal conversion efficiency can be simultaneously enhanced by the rational optimization of donor-acceptor groups, heavy atom number, and their functional positions, which can effectively decrease the energy gap between the singlet and triplet states and increase the spin-orbit coupling constant. Finally, efficient PTA were obtained that showed excellent performance in multimode-imaging-guided synergetic photodynamic/photothermal therapy. This study therefore expands the intrinsic mechanism of organic PTA and should help guide the rational design of future organic PTA via perturbation theory.

Ultrasensitive electrochemical immunosensor for quantitative detection of SCCA using Co3O4@CeO2-Au@Pt nanocomposite as enzyme-mimetic labels.

Recently early diagnosis of squamous cell carcinoma antigen (SCCA) as a tumor maker of various cancers has increasingly attracted a lot of attention with heightening of incidence rate of cancer. The SCCA with low concentration in human serum should be diluted before detecting. Thus, an immunoassay with high sensitivity is significant for early detecting SCCA. Therefore, a nonenzymatic sandwich-type electrochemical immunosensor herein was conducted to quantitative detection of squamous cell carcinoma antigen (SCCA). The amino functionalized cobaltosic oxide @ ceric dioxide nanocubes with core-shell morphology were prepared to combine sea-urchin like gold @ platinum nanoparticles (Co3O4@CeO2-Au@Pt), and used as labels to conjugate with secondary antibodies for signal amplification. Due to the synergetic effect, excellent electrochemical property and superior auxiliary catalytic activity of Co3O4@CeO2-Au@Pt, high electrocatalytic current responses toward the reduction of hydrogen peroxide (H2O2) were achieved. Besides, the electrodeposited gold nanoparticles (D-Au NPs) which were modified on glassy carbon electrodes (GCE) were used as antibodies carriers and sensing platforms. With the well cooperation of Co3O4@CeO2-Au@Pt and D-Au NPs, a broad linear range from 100fg/mL to 80ng/mL with a low detection limit of 33 fg/mL for detecting SCCA was achieved. In addition, the immunosensor displayed with good reproducibility, high selectivity and stability. The results are satisfactory when the proposed method has been applied to analyze human serum samples, indicating that the potential application is promising in clinical monitoring of tumor markers.

An ultrasensitive sandwich-type electrochemical immunosensor based on the signal amplification system of double-deck gold film and thionine unite with platinum nanowire inlaid globular SBA-15 microsphere.

A novel thionine unites with platinum nanowire inlaid globular SBA-15 (Pt NWs@g-SBA-15/Thi) not only utilizes as an efficient electrical signal probe but also constitutes an amplifying system with double-deck gold film (D-Au film) have been applied to the fabrication of sandwich-type immunosensor for detecting hepatitis B surface antigen (HBs Ag). The D-Au film can accelerate the electron transfer on the electrode interface due to the tunneling effect between the two Au films and can improve the load capacity of primary antibodies (Ab1) because of the good biocompatibility. The Pt NWs@g-SBA-15/Thi with uniform globular morphology not only can effectively reduce the spatial limitation for loading the secondary antibodies (Ab2) but also can provide outstanding pore accessibility of guest species from outside and offer catalytically active sites in a large scale. Besides, the presence of Thi can well enhance the electrical conductivity of Pt NWs@g-SBA-15/Thi. With the good cooperation between D-Au film and Pt NWs@g-SBA-15/Thi, a linear relationship between current signals and the concentrations of HBs Ag was obtained in the wide range from 10 fg/mL to 100ng/mL and the detection limit of HBs Ag was 3.3 fg/mL (signal-to-noise ratio of 3). Furthermore, the designed immunosensor with excellent selectivity, reproducibility and stability shows excellent performance in detection of human serum samples and provides a promising capacity for detecting a wide range of other tumor markers in clinical application.

A novel sandwich-type electrochemical immunosensor for PSA detection based on PtCu bimetallic hybrid (2D/2D) rGO/g-C3N4.

In this work, a sensitive sandwich-type electrochemical immunosensor was designed for the quantitative detection of prostate-specific antigen (PSA) by amperometric i-t. The Au loaded on thionine functionalized graphene oxide (Au@Th/GO) was used as a platform to immobilize primary antibodies (Ab1) and accelerate the electron transfer on the electrode interface. PtCu bimetallic hybrid were loaded on 2D/2D reduced graphene oxide/graphitic carbon nitride (PtCu@rGO/g-C3N4) with large surface area and biocompatibility, which were employed as labels for combining secondary antibodies (Ab2) and amplifying signals to improve the sensitivity of the designed immunosensor which attributes to its good activity for the reduction of hydrogen peroxide (H2O2). Under optimal conditions, the designed immunosensor exhibited a linear concentration range from 50fg/mL to 40ng/mL, with a low detection limit of 16.6fg/mL (S/N=3) for PSA. Additionally, the designed immunosensor showed acceptable selectivity, reproducibility and stability. The satisfactory results in analyze human serum samples indicated potential application promising in clinical monitoring of tumor markers.

An ultrasensitive sandwich-type electrochemical immunosensor based on the signal amplification strategy of mesoporous core-shell Pd@Pt nanoparticles/amino group functionalized graphene nanocomposite.

Herein, a novel and sensitive sandwich-type electrochemical immunosensor was fabricated for quantitative monitoring of prostate specific antigen (PSA). The sulfo group functionalized multi-walled carbon nanotubes (MWCNTs-SO3H) were used as substrate material to increase the specific surface area and enhance the conductivity of the glassy carbon electrode. Gold nanoparticles (Au NPs) were introduced to enhance the load capacity of the substrate material for primary antibodies (Ab1) and accelerate the electron transfer on the electrode interface. The mesoporous core-shell Pd@Pt nanoparticle loaded by amino group functionalized graphene (M-Pd@Pt/NH2-GS) with high specific surface area, high indexed facets, and good biocompatibility was not only as the carriers of secondary antibodies (Ab2) but also catalyzed the reduction of hydrogen peroxide (H2O2), which effectually amplified the current signal in detection of PSA. The as-proposed immunosensor exhibited high sensitivity and stability on the detection of PSA. A linear relationship between current signals and the concentrations of PSA was obtained in the range from 10fg/mL to 50ng/mL and the detection limit of PSA was 3.3fg/mL (signal-to-noise ratio of 3). Furthermore, the as-proposed immunosensor showed excellent performance in detection of human serum samples. The results suggest that the proposed immunosensor will be promising in the diagnostics application for accurately quantitative detection of PSA.