The antitumor activity of disulfiram (DSF), a traditional US Food and Drug Administration-approved drug for the treatment of “alcohol-dependence”, is Cu2+-dependent, but the intrinsic anfractuous ...biodistribution of copper in the human body and copper toxicity induced by exogenous copper supply have severely hindered its in vivo application. Herein, we report an in situ Cu2+ chelation-enhanced DSF-based cancer chemotherapy technique, using a tumor-specific “nontoxicity-to-toxicity” transition strategy based on hollow mesoporous silica nanoparticles as the functional carrier. Cu2+-doped, DSF-loaded hollow mesoporous silica nanoparticles were constructed for the rapid release of Cu2+ ions induced by the mild acidic conditions of the tumor microenvironment. This resulted in the rapid biodegradation of the nanoparticles and accelerated DSF release once the particles were endocytosed into tumor cells. The resulting in situ chelation reaction between the coreleased Cu2+ ions and DSF generated toxic CuET products and concurrently, Fenton-like reactions between the generated Cu+ ions and the high levels of H2O2 resulted in the production of reactive oxygen species (ROS) in the acidic tumor microenvironment. Both in vitro cellular assays and in vivo tumor-xenograft experiments demonstrated the efficient Cu-enhanced and tumor-specific chemotherapeutic efficacy of DSF, with cocontributions from highly toxic CuET complexes and ROS generated within tumors. This work provides a conceptual advancement of nanoparticle-enabled “nontoxicity-to-toxicity” transformation in tumors, to achieving high chemotherapeutic efficacy and biosafety.
Chemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the ...non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible.
The potential of the cluster regularly interspaced short palindromic repeat (CRISPR)‐associated protein 9 (Cas9)‐based therapeutic genome editing is severely hampered by the difficulties in precise ...regulation of the in vivo activity of the CRISPR‐Cas9 system. Herein, sono‐controllable and reactive oxygen species (ROS)‐sensitive sonosensitizer‐integrated metal–organic frameworks (MOFs), denoted as P/M@CasMTH1, are developed for augmented sonodynamic therapy (SDT) efficacy using the genome‐editing technology. P/M@CasMTH1 nanoparticles comprise singlet oxygen (1O2)‐generating MOF structures anchored with CRISPR‐Cas9 systems via 1O2‐cleavable linkers, which serve not only as a delivery vector of CRISPR‐Cas9 targeting MTH1, but also as a sonoregulator to spatiotemporally activate the genome editing. P/M@CasMTH1 escapes from the lysosomes, harvests the ultrasound (US) energy and converts it into abundant 1O2 to induce SDT. The generated ROS subsequently trigger cleavage of ROS‐responsive thioether bonds, thus inducing controllable release of the CRISPR‐Cas9 system and initiation of genome editing. The genomic disruption of MTH1 conspicuously augments the therapeutic efficacy of SDT by destroying the self‐defense system in tumor cells, thereby causing cellular apoptosis and tumor suppression. This therapeutic strategy for synergistic MTH1 disruption and abundant 1O2 generation provides a paradigm for augmenting SDT efficacy based on the emerging nanomedicine‐enabled genome‐editing technology.
A novel avenue to circumvent the resistance of tumor cells in conventional sonodynamic therapy is pioneered in this work, where targeted delivery and controllable release of the cluster regularly interspaced short palindromic repeat‐associated protein system is also achieved.
Elevating intratumoral levels of highly toxic reactive oxygen species (ROS) by nanocatalytic medicine for tumor‐specific therapy without using conventional toxic chemodrugs is recently of ...considerable interest, which, however, still suffers from less satisfactory therapeutic efficacy due to the relatively poor accumulation at the tumor site and largely blocked intratumoral infiltration of nanomedicines. Herein, an ultrasound (US)‐triggered dual size/charge‐switchable nanocatalytic medicine, designated as Cu‐LDH/HMME@Lips, is constructed for deep solid tumor therapy via catalytic ROS generations. The negatively charged liposome outer‐layer of the nanomedicine enables much‐prolonged blood circulation for significantly enhanced tumoral accumulation, while the positively charged Fenton‐like catalyst Cu‐LDH released from the liposome under the US stimulation demonstrates much enhanced intratumoral penetration via transcytosis. In the meantime, the co‐released sonosensitizer hematoporphyrin monomethyl ether (HMME) catalyze the singlet oxygen (1O2) generation upon the US irradiation, and deep‐tumoral infiltrated Cu‐LDH catalyzes the H2O2 decomposition to produce highly toxic hydroxyl radical (·OH) specifically within the mildly acidic tumor microenvironment (TME). The efficient intratumoral accumulation and penetration via the dual size/charge switching mechanism, and the ROS generations by both sonosensitization and Fenton‐like reactions, ensures the high therapeutic efficacy for the deep tumor therapy by the nanocatalytic medicine.
This work provides a novel ultrasound (US)‐triggered dual size/charge‐switchable nanocatalytic medicine for deep solid tumor therapy by reactive oxygen species generation in responses to both the US and tumor microenvironment (TME), which is believed to provide a feasible and promising strategy for catalytic tumor‐specific therapy.
Understanding the heterogeneous distribution of soil organic carbon (C) (SOC) in different soil environments is essential for predicting SOC preservation. However, SOC distribution differs in profile ...scales and molecular levels in various farmland soils, making it challenging to elucidate the environmental behaviors of SOC. In the present study, upland and paddy soil samples were both collected at different depths (0–100 cm) from an alluvial plain in the Pearl River Delta of South China. Wet chemistry experiments coupled with 13C-nuclear magnetic resonance (NMR) and spherical aberration correction scanning transmission electron microscopy (Cs-STEM) were used to determine the vertical distribution, chemical composition, and nano-scale sequestration mechanisms of SOC in upland and paddy soils. SOC content for upland soil, which was highest at the depth of 0–20 cm (6.98 ± 0.34 g·kg−1), decreased with increasing soil depth, while that of paddy soil had the highest content at a depth of 80–100 cm (86.66 ± 5.26 g·kg−1). Statistical analysis revealed that mineral-associated organic C (MAOC) in the upland soil and particulate organic C (POC) in the paddy soil were the major C fractions that were related to SOC content. Further analysis of NMR spectra showed that the molecular composition of upland SOC differs vertically, while the molecular composition and proportion of organic C in paddy soil varied with soil depth. Cs-STEM results revealed that the relative percentage of carboxyl C decreased from 0 to 20 cm (42.1%) to 80–100 cm (28.8%) with an increase in aromatic C from 7.7 to 27.2% for the upland soil, while the four C species showed similar abundance for paddy soil at different depths, consistent with the NMR results. Overall, the upland SOC was not as easily mineralized as that of paddy soil due to a lower percentage of easily oxidized carbon, higher percentage of MAOC, and higher decomposition degree. The results of this study would enrich our quantitative understanding of the profile distribution and chemical diversity of SOC from macro to micro scales in the alluvial plain from South China, and provide insights into C preservation in natural soils.
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•Paddy/upland SOC increases/decreases with increasing soil depth within 0–100 cm.•The deep SOC in paddy was more easily oxidized than that of the topsoil.•MAOC in upland and POC in paddy were strongly context dependent with SOC.•Decomposition degree of SOM was higher in upland than that in paddy.
Understanding the heterogeneous distribution of soil organic matter (SOM) on soil particles is essential for predicting the stability of organic carbon (C) in soil, but direct visualization of the ...microscopic distribution of organic C in soil is still challenging due to the complexity of soil particles. In this study, a paddy soil was fractionated and spherical aberration corrected scanning transmission electron microscopy (Cs-STEM) coupled with electron energy loss spectroscopy (EELS) was employed to analyze the microscopic distribution of organic C species on clay-sized soil particles (<2000 nm) from the different size fractions (800–2000 nm, 100–800 nm and 0–100 nm) at the nano and sub-nano scale. The EELS results demonstrated that the relative abundance of both phenolic and aliphatic C was quite independent of the particle size fractions, while aromatic and carboxyl carbon demonstrated the largest variations between fractions. With the decrease in soil particle size from 800 to 2000 nm to 0–100 nm, the median abundance of carboxyl (oxidized) C increased from 23% to 35%, and aromatic (reduced) C decreased accordingly from 40% to 16%. The statistical analysis demonstrated that the local organic C concentration was the major factor accounting for the variations in oxidized and reduced C species in soil particles, in which selective sorption of the organic C abundant of acidic functional groups by reactive minerals was responsible for the enrichment of oxidized C in small clay size soil particles. Overall, the results of this study contribute to an improved understanding of the chemical diversity of SOM in organo-mineral interfaces and provide insights in the microscopic C stabilization mechanisms in natural soils.
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•Distribution of SOM at different sized soil clay particles was unveiled by Cs-STEM.•Heterogeneity of organic C species was visualized at the nano and sub-nano scales.•Aromatic and carboxyl C showed significant variations among soil clay fractions.•Local organic C concentration determined chemical heterogeneity of organic C species.
Cadmium (Cd) contamination in soil-rice systems has become a global public concern. However, influencing factors and the contamination threshold of Cd in soils remain largely unknown owing to soil ...heterogeneity, which limits our ability to assess the risk to human health and to draft appropriate environmental policies. In this study, we selected the soil-rice system of Longtang and Shijiao town in southern China, which was characterized by multi-metal acidic soil contamination due to improper electronic waste recycling activities, as a case to analyze the influence of different soil properties on the Cd threshold in the soil and Cd accumulation in rice. The results showed that soil organic matter (SOM) was the main factor regulating Cd accumulation in the soil-rice system. Moreover, compared with the total Cd concentration, the DTPA-extractable Cd concentration in the soil was a better predictor of Cd transportation in the soil-rice system. According to the prediction model, when SOM was < 35 g kg−1, the CdDTPA threshold was 0.16 mg kg−1 with a 95% likelihood of Cdrice accumulation above the Chinese food standard limit (0.2 mg kg−1). Conversely, when SOM was ≥ 35 g kg−1, the CdDTPA threshold was only 0.03 mg kg−1. This study of the influence of SOM on Cd accumulation in a soil-rice system confirms that SOM is a crucial parameter for better and safer rice production, especially in multi-metal contaminated acidic soils.
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•Path analysis showed better identification of factors regulating Cd transportation.•SOM was the main factor regulating Cd accumulation in soil-rice systems.•Soil DTPA-extractable Cd concentration was predictive of Cd transportation.•The regional CdDTPA threshold was 0.16 mg kg−1 with SOM <35 g kg−1.•The regional CdDTPA threshold was 0.03 mg kg−1 with SOM ≥35 g kg−1.
Recently, visual number sense has been identified from deep neural networks (DNNs). However, whether DNNs have the same capacity for real-world scenes, rather than the simple geometric figures that ...are often tested, is unclear. In this study, we explore the number perception of scenes using AlexNet and find that numerosity can be represented by the pattern of group activation of the category layer units. The global activation of these units increases with the number of objects in the scene, and the variations in their activation decrease accordingly. By decoding the numerosity from this pattern, we reveal that the embedding coefficient of a scene determines the likelihood of potential objects to contribute to numerical perception. This was demonstrated by the more optimized performance for pictures with relatively high embedding coefficients in both DNNs and humans. This study for the first time shows that a distinct feature in visual environments, revealed by DNNs, can modulate human perception, supported by a group-coding mechanism.
With the development of infrared monitoring and early warning system, more and more attention has been paid to the research of infrared small target detection. How to effectively detect the target in ...a complex background has always been a major challenge for researchers. This paper presents a space-time-based detection for small infrared target, which can improve the performance of infrared small target detection system. Firstly, the targets are enhanced and the background clutter is suppressed by the morphological filter. Then, the segmentation images method is proposed to erase the majority noises, which calculates an adaptive thresholds based on the constant false alarm rate (CFAR). Finally, a dynamic detection is proposed to erase all of the noises in the multi-frame, which adjust the size and position of the search window based on the kinematic rule of targets. Experimental results show that this technology can effectively detect the small infrared target with high performance.
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