H2O2-triggered controllable carbon monoxide delivery for photothermally augmented gas therapy.

Carbon monoxide (CO) gas therapy has shown great potential as a very promising approach in the ongoing fight against tumors. However, delivering unstable CO to the tumor site and safely releasing it for maximum efficacy still have unsatisfactory outcomes. In this study, we've developed nanotheranostics (IN-DPPCO NPs) based on conjugated polymer IN-DPP and carbon monoxide (CO) carrier polymer mPEG(CO) for photothermal augmented gas therapy. The IN-DPPCO NPs can release CO with the hydrogen peroxide (H2O2) overexpressed in the tumor microenvironment. Meanwhile, IN-DPPCO NPs exhibit strong absorption in the near-infrared window, showing a high photothermal conversion efficiency of up to 41.5% under 808 nm laser irradiation. In vitro and in vivo experiments demonstrate that these nanotheranostics exhibit good biocompatibility. Furthermore, the synergistic CO/photothermal therapy shows enhanced therapeutic efficacy compared to gas therapy alone. This work highlights the great promise of conjugated polymer nanoparticles as versatile nanocarriers for spatiotemporally controlled and on-demand delivery of gaseous messengers to achieve precision cancer theranostics.

The impact of green finance policy on green innovation performance: Evidence from Chinese heavily polluting enterprises.

Green innovation (GI) is increasingly recognised as an effective strategy for tackling climate change, mitigating environmental issues, and promoting sustainable development. Using panel data of the Chinese listed firms from 2007 to 2019, this study adopts the difference-in-differences approach to assess the impact of the green finance policy (GFP) initiated by the Chinese government in 2012 on the green innovation performance of firms. The findings reveal that the GFP significantly boosts the green innovation performance of heavily polluting enterprises (HPEs). Notably, this effect is more pronounced in state-owned enterprises and firms with high dependence on external finance. Compared with penalty-based regulations, incentive-based and voluntary environmental regulations demonstrate more significant moderating effects on the relationship between the GFP and green innovation performance for HPEs. We also identify improved efficiency in the usage of green investments as a potential mechanism through which the GFP enhances the green innovation performance of HPEs. Further comparative analysis shows that green enterprises can achieve simultaneous improvement in both the quality and quantity of green innovation, whereas HPEs predominantly exhibit enhancements in innovation quantity. To maximise the GFP's positive effects, it is recommended to facilitate more targeted bank lending towards HPEs to support their structural transformation. Additionally, the coordinated deployment of diverse environmental policy instruments is advised to exploit their synergistic effects.

Conjugated Polymeric Materials in Biological Imaging and Cancer Therapy.

Conjugated polymers (CPs) have attracted much attention in the fields of chemistry, medicine, life science, and material science. Researchers have carried out a series of innovative researches and have made significant research progress regarding the unique photochemical and photophysical properties of CPs, expanding the application range of polymers. CPs are polymers formed by the conjugation of multiple repeating light-emitting units. Through precise control of their structure, functional molecules with different properties can be obtained. Fluorescence probes with different absorption and emission wavelengths can be obtained by changing the main chain structure. By modifying the side chain structure with water-soluble groups or selective recognition molecules, electrostatic interaction or specific binding with specific targets can be achieved; subsequently, the purpose of selective recognition can be achieved. This article reviews the research work of CPs in cell imaging, tumor diagnosis, and treatment in recent years, summarizes the latest progress in the application of CPs in imaging, tumor diagnosis, and treatment, and discusses the future development direction of CPs in cell imaging, tumor diagnosis, and treatment.

NIR-II Absorbing Conjugated Polymer Nanotheranostics for Thermal Initiated NO Enhanced Photothermal Therapy.

Photothermal therapy (PTT) has received constant attention as a promising cancer treatment. However, PTT-induced inflammation can limit its effectiveness. To address this shortcoming, we developed second near-infrared (NIR-II) light-activated nanotheranostics (CPNPBs), which include a thermosensitive nitric oxide (NO) donor (BNN6) to enhance PTT. Under a 1064 nm laser irradiation, the conjugated polymer in CPNPBs serves as a photothermal agent for photothermal conversion, and the generated heat triggers the decomposition of BNN6 to release NO. The combination of hyperthermia and NO generation under single NIR-II laser irradiation allows enhanced thermal ablation of tumors. Consequently, CPNPBs can be exploited as potential candidates for NO-enhanced PTT, holding great promise for their clinical translational development.

The impact of green technology innovation on carbon dioxide emissions: The role of local environmental regulations.

Environmental pollution has become a global issue attracting ever-increasing attention. Green technology innovation (GTI) is considered an effective strategy in countering this problem and helping achieve sustainability goals. However, the market failure suggests that intervention from the government is necessary to promote the effectiveness of technological innovation and hence, its positive social impacts on emissions reduction. This study investigates how the environmental regulation (ER) influences the relationship between green innovation and CO2 emissions reduction in China. Employing data from 30 provinces from the period 2003 to 2019, the Panel Fixed-effect model, the Spatial Durbin Model (SDM), the System Generalised Method of Moments (SYS-GMM) and the Difference-In-Difference (DID) models are applied to take issues relating to endogeneity and spatial impact into consideration. The results indicate that environmental regulations positively moderate the impact of green knowledge innovation (GKI) on CO2 emissions reduction but have a much weaker moderation effect when green process innovation (GPI) is considered. Among different types of regulatory instruments, investment-based regulation (IER) is the most effective in promoting the relationship between green innovation and emissions reduction, followed by command-and-control-based regulation (CER). Expenditure-based regulation (EER) is less effective and can encourage short-termism and opportunistic behaviour among firms, who can accept the paying of fines as a cheaper cost over the short-term than investment in green innovation. Moreover, the spatial spillover effect of green technological innovation on carbon emissions in neighbouring regions is confirmed, in particular when IER and CER are implemented. Lastly, the heterogeneity issue is further examined by considering differences in the economic development and the industrial structure across different regions, and the conclusions reached remain robust. This study identifies that the market-based regulatory instrument, IER, works best in promoting green innovation and emissions reduction among Chinese firms. It also encourages GKI which may assist firms in achieving long-term sustained growth. The study recommends further development of the green finance system to maximise the positive impact of this policy instrument.

A NIR fluorescence probe for monitoring Cys upregulation induced by balsam pear polysaccharide and imaging in zebrafish.

In this work, we introduced the acrylate recognition group into dicyanoisophorone derivative DCI-C-OH to construct the NIR fluorescent probe DCI-C-Cys with a large Stokes shift (240 nm). DCI-C-Cys could specifically respond to Cys, resulting in a 22-fold increase in fluorescence intensity at 702 nm. Meanwhile, the probe has the advantages of good water solubility, high sensitivity (93 nM), and excellent biocompatibility. Moreover, DCI-C-Cys successfully monitored endogenous and exogenous Cys in HepG2 cells and zebrafish. Most importantly, we found that balsam pear polysaccharide could lead to the increase of intracellular Cys levels, which might be conducive to the further study of the antioxidant mechanism of balsam pear polysaccharide.

Peroxymonosulfate activation by Co3O4/SnO2 for efficient degradation of ofloxacin under visible light.

In this work, Co3O4/SnO2 catalyst was prepared by a one-pot hydrothermal method and applied in the activation of peroxymonosulfate (PMS) for the degradation of the target pollutant ofloxacin (OFX). The results showed that the PMS/Co3O4/SnO2-8% system had a 92% OFX degradation efficiency after 30 min of catalytic reaction, which was 46 times higher than that of PMS/SnO2 alone, and the degradation efficiency could be maintained in a wide pH range (5-11). In addition, reactive oxygen species quenching experiments and electron spin resonance spectra confirmed that sulfate radicals, superoxide radicals, hydroxyl radicals and singlet oxygen were the dominant active groups. The excellent recyclability and stability of the as-prepared catalyst were confirmed by cycling experiments and characterization results. Finally, a possible degradation pathway of OFX was suggested, and the intermediate toxicity of this system was identified and analyzed by a quantitative structure-activity relationship (QSAR).

Red-emitting fluorescent turn-on probe with specific isothiocyanate recognition site for cysteine imaging in living systems.

Cysteine (Cys) is an effective biomarker in life systems and is closely related to a variety of diseases, so developing a specific and efficient detection method for Cys is of great significance. To date, extensive work has been undertaken toward this goal. However, the differentiation of Cys from other biothiols still represents a challenge from an experimental point of view. Toward this end, a selective and sensitive red-emitting probe (TMN-NCS) with an isothiocyanate (ITC)-based structure was proposed in this paper. A large Stokes shift (210 nm) was observed upon addition of Cys to a solution of TMN-NCS. In addition, TMN-NCS showed low toxicity, a low detection limit (120 nM), and excellent cell permeability. The results suggested that TMN-NCS holds great promise for biological applications.

Sodium fluoride activates the extrinsic apoptosis via regulating NOX4/ROS-mediated p53/DR5 signaling pathway in lung cells both in vitro and in vivo.

An extensive body of research has demonstrated that pulmonary toxicity induced by fluoride is related to cell apoptosis. Although induction of death receptor-initiated extrinsic apoptosis by sodium fluoride (NaF) has been reported, its mechanism of action is still not clearly defined. Herein, we found that NaF treatment induced activation of caspase-8 in BEAS-2B cells, resulting in apoptosis, which was markedly reduced by blocking caspase-8 using small interfering RNA (siRNA). In this study, we report that death receptor 5 (DR5), a major component of the extrinsic apoptotic pathway, is markedly induced upon NaF stimulation. Enhanced DR5 induction was necessary for the apoptotic effects of NaF, inasmuch as transfected BEAS-2B cells with DR5 siRNA attenuated NaF-induced caspase-8 activation in lung cells. Mechanism investigation indicated that the induction of DR5, following NaF exposure, was mediated by tumor protein 53 (p53)-dependent transcriptional activation. Notably, we demonstrated that NaF could induce a significant increase in intracellular reactive oxygen species (ROS) level derived from nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). Specifically, NOX4 knockdown inhibited NaF-induced the activation of p53/DR5 axis by reducing NOX4-derived ROS production. Further in vivo investigation demonstrated that NOX4 deficiency markedly attenuates NaF-induced lung injury, apoptosis, and ROS levels in the lung. Moreover, the expressions of p53 and DR5 were significantly reduced after NaF treatment in NOX4 knockout mice compared with the wild type mice. Taken together, our findings provide a novel insight into for the pulmonary apoptosis in response to NaF exposure.

A novel NIR fluorescence probe with cysteine-activated structure for specific detection of cysteine and its application in vitro and in vivo.

Cysteine (Cys) as a vital antioxidant molecule and an effective biomarker for illness, plays an essential role in physiological functions and pathological processes. Extensive work has been done to explore the physiological functions of Cys and develop probes for detection of biothiols. However, the challenge to differentiate Cys from glutathione and homocystine remains. In this work, we constructed a novel near-infrared (NIR) probe, termed TMN-Cys, using TMN-NH2 and thionoesters. The probe could selectively detect Cys over homocysteine and glutathione in solution. It displayed a large Stokes shift (210 nm) upon treatment with Cys, and its detection limit was as low as 79 nM. Moreover, this probe showed low toxicity and was successfully employed in monitoring endogenous Cys in living cells and mice.

Cardamonin induces G2/M arrest and apoptosis via activation of the JNK-FOXO3a pathway in breast cancer cells.

Cardamonin (CD), a naturally occurring chalcone isolated from large black cardamom, was previously reported to suppress the proliferation of breast cancer cells. However, its precise molecular anti-tumor mechanisms have not been well elucidated. In this study, we found that CD markedly inhibited the proliferation of MDA-MB 231 and MCF-7 breast cancer cells through the induction of G2/M arrest and apoptosis. Reactive oxygen species (ROS) plays a pivotal role in the inhibition of CD-induced cell proliferation. Treatment with N-acetyl-cysteine (NAC), an ROS scavenger, blocked CD-induced G2/M arrest and apoptosis in this study. Quenching of ROS by overexpression of catalase also blocked CD-induced cell cycle arrest and apoptosis. We showed that CD enhanced the expression and nuclear translocation of Forkhead box O3 (FOXO3a) via upstream c-Jun N-terminal kinase, inducing the expression of FOXO3a and its target genes, including p21, p27, and Bim. This process led to the reduction of cyclin D1 and enhancement of activated caspase-3 expression. The addition of NAC markedly reversed these effects, knockdown of FOXO3a using small interfering RNA also decreased CD-induced G2/M arrest and apoptosis. In vivo, CD efficiently suppressed the growth of MDA-MB 231 breast cancer xenograft tumors. Taken together, our data provide a molecular mechanistic rationale for CD-induced cell cycle arrest and apoptosis in breast cancer cells.

Engineering biocompatible benzodithiophene-based polymer dots with tunable absorptions as high-efficiency theranostic agents for multiscale photoacoustic imaging-guided photothermal therapy.

To date, photoacoustic imaging (PAI) and PAI-guided photothermal therapy (PTT) have been performed for noninvasive cancer diagnosis and precise ablation of tumors. To conduct concurrent PAI and PTT, it is essential to develop theranostic agents with strong optical absorption and high photothermal transfer efficiency. In this study, we have engineered theranostic agents with tunable absorptions based on conjugated polymer dots (Pdots) with different structures via the simple precipitation method. The as-synthesized Pdots exhibit strong absorption, high biocompatibility, and superior stability. In addition, the Pdots demonstrate that they can serve as contrast agents for multiscale PAI in vitro and in vivo. More importantly, a high photothermal conversion efficiency up to 40% is reached under irradiation with LED light, resulting in effective cancer treatment with extremely low light dose. Consequently, they show the potential as imaging-guided therapeutic agents for clinical cancer treatment and various biomedical applications.

Highly Stable Conjugated Polymer Dots as Multifunctional Agents for Photoacoustic Imaging-Guided Photothermal Therapy.

Theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, most photothermal agents are limited by their instability and low photothermal conversion efficiency. In this study, we report new conjugated polymer dots (Pdots) as multifunctional agents for photoacoustic (PA) imaging-guided PTT. The novel 4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene-6,6'-dibromo-N,N'-(2-ethylhexyl)isoindigo (BDT-IID) Pdots are readily fabricated though nanoreprecipitation and can absorb strongly in the 650-700 nm region. Furthermore, the BDT-IID Pdots possess a stable nanostructure and an extremely low biotoxicity. In particular, its photothermal conversion efficiency can be up to 45%. More importantly, our in vivo results exhibit that the BDT-IID Pdots are able to offer concurrently enhanced PA contrast and sufficient photothermal effect. Consequently, the BDT-IID Pdots can be exploited as a unique theranostic nanoplatform for PA imaging-guided PTT of tumors, holding great promise for their clinical translational development.

Increasing the doping efficiency by surface energy control for ultra-transparent graphene conductors.

Graphene's attractiveness in many applications is limited by its high resistance. Extrinsic doping has shown promise to overcome this challenge but graphene's performance remains below industry requirements. This issue is caused by a limited charge transfer efficiency (CTE) between dopant and graphene. Using AuCl3 as a model system, we measure CTE as low as 5% of the expected values due to the geometrical capacitance of small adsorbate clusters. We here demonstrate a strategy for enhancing the CTE by a two-step optimization of graphene's surface energy prior to AuCl3 doping. First, exposure to UV ozone modified the hydrophilicity of graphene and was found to decrease the cluster's geometric capacitance, which had a direct effect on the CTE. Occurrence of lattice defects at high UV exposure, however, deteriorated graphene's transport characteristics and limited the effectiveness of this pretreatment step. Thus, prior to UV exposure, a functionalized polymer layer was introduced that could further enhance graphene's surface energy while protecting it from damage. Combination of these treatment steps were found to increase the AuCl3 charge transfer efficiency to 70% and lower the sheet resistance to 106 Ω/γ at 97% transmittance which represents the highest reported performance for doped single layer graphene and is on par with commercially available transparent conductors.

Highly absorbing multispectral near-infrared polymer nanoparticles from one conjugated backbone for photoacoustic imaging and photothermal therapy.

Semiconducting polymers with specific absorption are useful in various applications, including organic optoelectronics, optical imaging, and nanomedicine. However, the optical absorption of a semiconducting polymer with a determined structure is hardly tunable when compared with that of inorganic semiconductors. In this work, we show that the optical absorption of polymer nanoparticles from one conjugated backbone can be effectively tuned through judicious design of the particle morphology and the persistence length of polymers. Highly absorbing near-infrared (NIR) polymers based on diketopyrrolopyrrole-dithiophene (DPP-DT) are synthesized to have different molecular weights (MWs). The DPP-DT polymer with a large molecular weight and high persistence length exhibited remarkably high optical absorption with a peak mass extinction coefficient of 81.7 L g-1 cm-1, which is one of the highest value among various photothermal agents reported to date. Particularly, the polymer nanoparticles with different sizes exhibit broadly tunable NIR absorption peaks from 630 to 811 nm. The PEGylated small polymer dots (Pdots) show good NIR light-harvesting efficiency and high non-radiative decay rates, resulting in a relatively high photothermal conversion efficiency in excess of 50%. Thus, this Pdot-based platform can serve as promising photothermal agents and photoacoustic probes for cancer theranostics.

Enhanced Phototherapy by Nanoparticle-Enzyme via Generation and Photolysis of Hydrogen Peroxide.

Light has been widely used for cancer therapeutics such as photodynamic therapy (PDT) and photothermal therapy. This paper describes a strategy called enzyme-enhanced phototherapy (EEPT) for cancer treatment. We constructed a nanoparticle platform by covalent conjugation of glucose oxidase (GOx) to small polymer dots, which could be persistently immobilized into a tumor. While the malignant tumors have high glucose uptake, the GOx efficiently catalyzes the glucose oxidation with simultaneous generation of H2O2. Under light irradiation, the in situ generated H2O2 was photolyzed to produce hydroxyl radical, the most reactive oxygen species, for killing cancer cells. In vitro assays indicated that the cancer cells were destroyed by using a nanoparticle concentration at 0.2 µg/mL and a light dose of ∼120 J/cm2, indicating the significantly enhanced efficiency of the EEPT method when compared to typical PDT that requires a photosensitizer of >10 µg/mL for effective cell killing under the same light dose. Furthermore, remarkable inhibition of tumor growth was observed in xenograft-bearing mice, indicating the promise of the EEPT approach for cancer therapeutics.

Photo-Cross-Linkable Polymer Dots with Stable Sensitizer Loading and Amplified Singlet Oxygen Generation for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising treatment modality for clinical cancer therapy. However, the therapeutic effect of PDT is strongly dependent on the property of photosensitizer. Here, we developed photo-cross-linkable semiconductor polymer dots doped with photosensitizer Chlorin e6 (Ce6) to construct a nanoparticle platform for photodynamic therapy. Photoreactive oxetane groups were attached to the side chains of the semiconductor polymer. After photo-cross-linking reaction, the Ce6-doped Pdots formed an interpenetrated structure to prevent Ce6 leaching out from the Pdot matrix. Spectroscopic characterizations revealed an efficient energy transfer from the polymer to Ce6 molecules, resulting in amplified generation of singlet oxygen. We evaluated the cellular uptake, cytotoxicity, and photodynamic effect of the Pdots in gastric adenocarcinoma cells. In vitro photodynamic experiments indicated that the Ce6-doped Pdots (∼10 µg/mL) effectively killed the cancer cells under low dose of light irradiation (∼60 J/cm2). Furthermore, in vivo photodynamic experiments were carried out in tumor-bearing nude mice, which indicated that the Pdot photosensitizer apparently suppressed the growth of solid tumors. Our results demonstrate that the photo-cross-linkable Pdots doped with photosensitizer are promising for photodynamic cancer treatment.

Incorporation of Porphyrin to π-Conjugated Backbone for Polymer-Dot-Sensitized Photodynamic Therapy.

The photosensitizers used in photodynamic therapy are mainly based on porphyrin derivatives. However, clinical applications encounter several limitations regarding photosensitizers such as their low absorption coefficients, poor water-solubility, and leaching from delivery carriers. Here, we describe covalent incorporation of porphyrin in conjugated polymer backbone for development of efficient polymer-dot photosensitizer. Spectroscopic characterizations revealed that the light-harvesting polymer dominantly transfer the excitation energy to the porphyrin unit, yielding efficient singlet oxygen generation for photodynamic therapy. The polymer dots (Pdots) also possess excellent stability that overcomes the photosensitizer leaching problem as encountered in other nanoparticle carriers. In vitro cytotoxicity and photodynamic efficacy of the Pdots were evaluated in MCF-7 cells by in vitro assay, indicating that the Pdots can efficiently damage cancer cells. In vivo photodynamic therapy by using the Pdots was further investigated with xenograft tumors in Balb/c nude mice, which show that the tumors were significantly inhibited or eradicated in certain cases. The high-yield singlet oxygen generation and excellent stability of porphyrin-incorporated Pdots are promising for photodynamic treatment of malignant tumors.

Amplified Singlet Oxygen Generation in Semiconductor Polymer Dots for Photodynamic Cancer Therapy.

This paper described the energy-transfer amplified singlet oxygen generation in semiconductor polymer dots (Pdots) for in vitro and in vivo photodynamic therapy. Hydrophobic photosensitizer tetraphenylporphyrin was facilely doped in the nanoparticles consisting of densely packed semiconductor polymers. Optical characterizations indicated that the fluorescence of Pdots was completely quenched by the photosensitizer, yielding an energy transfer efficiency of nearly 100% and singlet-oxygen generation quantum yield of ∼50%. We evaluated the cellular uptake, dark toxicity, and photodynamic therapy of the Pdot photosensizer in human gastric adenocarcinoma cells. The in vitro studies indicated that cancer cells were efficiently destroyed at very low dose of the Pdots such as 1 µg/mL by using the light dose of 90 J/cm(2), which is considerably less than that in clinical practice. The antitumor effect of the Pdots was further evaluated in vivo with human gastric adenocarcinoma xenografts in Balb/c nude mice, which show that the xenograft tumors were significantly inhibited and eradicated in some cases. Our results indicate the energy transfer amplified Pdot platforms have great therapeutic potential for treating malignant cancers.

Dopant morphology as the factor limiting graphene conductivity.

Graphene's low intrinsic carrier concentration necessitates extrinsic doping to enhance its conductivity and improve its performance for application as electrodes or transparent conductors. Despite this importance limited knowledge of the doping process at application-relevant conditions exists. Employing in-situ carrier transport and Raman characterization of different dopants, we here explore the fundamental mechanisms limiting the effectiveness of doping at different doping levels. Three distinct transport regimes for increasing dopant concentration could be identified. First the agglomeration of dopants into clusters provides a route to increase the graphene conductivity through formation of ordered scatterers. As the cluster grows, the charge transfer efficiency between graphene and additional dopants decreases due to emerging polarization effects. Finally, large dopant clusters hinder the carrier motion and cause percolative transport that leads to an unexpected change of the Hall effect. The presented results help identifying the range of beneficial doping density and guide the choice of suitable dopants for graphene's future applications.