Recent Progress on Second Near-Infrared Emitting Carbon Dots in Biomedicine.

Second near-infrared (NIR-II) carbon dots, with absorption or emission between 1000 and 1700 nm, are gaining increasing attention in the biomaterial field due to their distinctive properties, which include straightforward preparation processes, stable photophysical characteristics, excellent biocompatibility, and low cost. As a result, there is a growing focus on the controlled synthesis and modulation of the photochemical and photophysical properties of NIR-II carbon dots, with the aim to further expand their biomedical applications, a current research hotspot. This account aims to provide a comprehensive overview of the recent advancements in NIR-II carbon dots within the biomedical field. The review will cover the following topics: (i) the design, synthesis, and purification of NIR-II carbon dots, (ii) the surface modification strategies, and (iii) the biomedical applications, particularly in the domain of cancer theranostics. Additionally, this account addresses the challenges encountered by NIR-II carbon dots and will outline future directions in the realm of cancer theranostics. By exploring carbon-based NIR-II biomaterials, we can anticipate that this contribution will garner increased attention and contribute to the development of next-generation advanced functional carbon dots, thereby offering enhanced tools and strategies in the biomedical field.

In situ fabrication of sporoid-like flexible electrodes via Fe-regulated electron density for highly efficient and ultra-stable overall seawater splitting.

Construction of ultra-stable, flexible, efficient and economical catalytic electrodes is of great significance for the seawater electrolysis for hydrogen production. This work is grounded in a one-step mild electroless plating method to construct industrial-grade super-stable overall water splitting (OWS) catalytic electrodes (Fe1-Ni1P@GF) by growing loose and porous spore-like Fe1-Ni1P conductive catalysts in situ on flexible glass fibre (GF) insulating substrates with precise elemental regulation. Cost-effective Fe regulation boosts the electronic conductivity and charge transfer ability to achieve the construction of high intrinsic activity and strong electron density electrodes. Fe1-Ni1P@GF exhibits remarkable catalytic performance in hydrogen and oxygen evolution reaction (HER and OER), providing current densities of 10 mA cm-2 for HER and 100 mA cm-2 for OER at overpotentials of 51 and 216 mV, respectively. Moreover, it achieves 10 mA cm-2 at 1.42 V for OWS, and exhibits stable operation for over 1440 h at 1000 mA cm-2 in quasi-industrial environment of 6.0 M KOH + 0.5 M NaCl, without any performance degradation. This strategy enables the preparation of universally applicable P-based electrodes (ternary, quaternary, etc.) and large-area flexible electrodes (paper or cotton), significantly expands the practicality of the electrodes and demonstrating promising potential for industrial applications.

CDs Regulated Sulfur-Based Flexible Electrode with Range pH Values for Efficient and Durable Hydrogen Evolution Reaction.

How to mildly structure a high intrinsic activity and stable catalytic electrode to realize long-term catalytic water splitting to produce hydrogen at a wide range of pH values at industrial high current is a challenge. Herein, this work creatively proposes to prepare industrial-grade catalytic electrodes with high efficiency and stability at high current density through carbon quantum dots (CDs) modification nickel sulfide on hydrophilic flexible filter paper via one-step mild chemical plating (denoted as CDs-Ni3 S2 @HFP). The intrinsic activity and surface area, electron transfer ability, and corrosion resistance of Ni3 S2 material are increased due to the regulation, homogenous, and high concentration doping of CDs. The overpotential of the flexible catalytic electrode is only 30, 35, and 87 mV in 1 m KOH, simulated seawater (1 m KOH + 0.5 m NaCl), and neutral electrolyte (0.5 m PBS) at a current density of 10 mA cm-2 . More attractively, the CDs-Ni3 S2 @HFP electrode achieves over 500 h of efficient and stable catalysis at industrial high current density (500 mA cm-2 ). Due to the advantages of mild, universal, and large-area preparation of catalytic materials, this work provides technical support for flexible catalytic electrodes in efficient catalysis toward water splitting, energy storage, and device preparation.

Recent Advances of Photoactive Near-Infrared Carbon Dots in Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential and highly required for cancer photodynamic therapy. Carbon dots (CDs), the rising star of carbon-based nanomaterial family, have shown great potential in cancer PDT benefiting from their excellent photoactivity, luminescence properties, low price, and biocompatibility. In recent years, photoactive near-infrared CDs (PNCDs) have attracted increasing interest in this field due to their deep therapeutic tissue penetration, superior imaging performance, excellent photoactivity, and photostability. In this review, we review recent progress in the designs, fabrication, and applications of PNCDs in cancer PDT. We also provide insights of future directions in accelerating the clinical progress of PNCDs.

Molecular elements: novel approaches for molecular building.

Classically, a molecular element (ME) is a pure substance composed of two or more atoms of the same element. However, MEs, in the context of this review, can be any molecules as elements bonded together into the backbone of synthetic oligonucleotides (ONs) with designed sequences and functions, including natural A, T, C, G, U, and unnatural bases. The use of MEs can facilitate the synthesis of designer molecules and smart materials. In particular, we discuss the landmarks associated with DNA structure and related technologies, as well as the extensive application of ONs, the ideal type of molecules for intervention therapy aimed at correcting disease-causing genetic errors (indels). It is herein concluded that the discovery of ON therapeutics and the fabrication of designer molecules or nanostructures depend on the ME concept that we previously published. Accordingly, ME will be our focal point as we discuss related research directions and perspectives in making molecules and materials. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.

Resolution of MoS2 Nanosheets-Induced Pulmonary Inflammation Driven by Nanoscale Intracellular Transformation and Extracellular-Vesicle Shuttles.

Pulmonary exposure to some engineered nanomaterials can cause chronic lesions as a result of unresolved inflammation. Among 2D nanomaterials and graphene, MoS2 has received tremendous attention in optoelectronics and nanomedicine. Here an integrated approach is proposed to follow up the transformation of MoS2 nanosheets at the nanoscale and assesss their impact on lung inflammation status over 1 month after a single inhalation in mice. Analysis of immune cells, alveolar macrophages, extracellular vesicles, and cytokine profiling in bronchoalveolar lavage fluid (BALF) shows that MoS2 nanosheets induced initiation of lung inflammation. However, the inflammation is rapidly resolved despite the persistence of various biotransformed molybdenum-based nanostructures in the alveolar macrophages and the extracellular vesicles for up to 1 month. Using in situ liquid phase transmission electron microscopy experiments, the dynamics of MoS2 nanosheets transformation triggered by reactive oxygen species could be evidenced. Three main transformation mechanisms are observed directly at the nanoscale level: 1) scrolling of the dispersed sheets leading to the formation of nanoscrolls and folded patches, 2) etching releasing soluble MoO4 - , and 3) oxidation generating oxidized sheet fragments. Extracellular vesicles released in BALF are also identified as a potential shuttle of MoS2 nanostructures and their degradation products and more importantly as mediators of inflammation resolution.

Mild construction of an Fe-B-O based flexible electrode toward highly efficient alkaline simulated seawater splitting.

It is essential to construct self-supporting electrodes based on earth-abundant iron borides in a mild and economical manner for grid-scale hydrogen production. Herein, a series of highly efficient, flexible, robust, and scalable Fe-B-O@FeBx modified on hydrophilic cloth (denoted as Fe-B-O@FeBx/HC, 10 cm × 10 cm) are fabricated by mild electroless plating. The overpotentials and Tafel slope values for the hydrogen and oxygen evolution reactions are 59 mV and 57.62 mV dec-1 and 181 mV and 65.44 mV dec-1, respectively; only 1.462 V is required to achieve 10 mA cm-2 during overall water splitting (OWS). Fe-B-O@FeBx/HC maintains its high catalytic activity for more than 7 days at an industrial current density (400 mA cm-2), owing to the loosened popcorn-like Fe-B-O@FeBx that is firmly loaded on a 2D-layered and mechanically robust substrate along with its fast charge and mass transfer kinetics. The chimney effect of core-shell borides@(oxyhydro)oxides enhances the OWS performance and protects the inner metal borides from further corrosion. Moreover, the flexible Fe-B-O@FeBx/HC electrode has a low cost for grid-scale hydrogen production ($2.97 kg-1). The proposed strategy lays a solid foundation for universal preparation, large-scale hydrogen production and practical applications thereof.

Combined Photothermal and Photodynamic Therapy for Cancer Treatment Using a Multifunctional Graphene Oxide.

Graphene oxide (GO) is one of the most studied nanomaterials in many fields, including the biomedical field. Most of the nanomaterials developed for drug delivery and phototherapies are based on noncovalent approaches that lead to an unspecific release of physisorbed molecules in complex biological environments. Therefore, preparing covalently functionalized GO using straightforward and versatile methods is highly valuable. Phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT), have shown great potential as effective therapeutic approaches against cancer. To overcome the limits of a single method, the combination of PTT and PDT can lead to a combined effect with a higher therapeutic efficiency. In this work, we prepare a folic acid (FA) and chlorin e6 (Ce6) double-functionalized GO for combined targeted PTT/PDT. This conjugate can penetrate rapidly into cancer cells and macrophages. A combined effect of PTT and PDT is observed, leading to a higher killing efficiency toward different types of cells involved in cancer and other diseases. Our work provides a simple protocol to prepare multifunctional platforms for the treatment of various diseases.

Comparative Effects of Graphene and Molybdenum Disulfide on Human Macrophage Toxicity.

Graphene and other 2D materials, such as molybdenum disulfide, have been increasingly used in electronics, composites, and biomedicine. In particular, MoS2 and graphene hybrids have attracted a great interest for applications in the biomedical research, therefore stimulating a pertinent investigation on their safety in immune cells like macrophages, which commonly engulf these materials. In this study, M1 and M2 macrophage viability and activation are mainly found to be unaffected by few-layer graphene (FLG) and MoS2 at doses up to 50 µg mL-1 . The uptake of both materials is confirmed by transmission electron microscopy, inductively coupled plasma mass spectrometry, and inductively coupled plasma atomic emission spectroscopy. Notably, both 2D materials increase the secretion of inflammatory cytokines in M1 macrophages. At the highest dose, FLG decreases CD206 expression while MoS2 decreases CD80 expression. CathB and CathL gene expressions are dose-dependently increased by both materials. Despite a minimal impact on the autophagic pathway, FLG is found to increase the expression of Atg5 and autophagic flux, as observed by Western blotting of LC3-II, in M1 macrophages. Overall, FLG and MoS2 are of little toxicity in human macrophages even though they are found to trigger cell stress and inflammatory responses.

Correction: Controlled functionalization of carbon nanodots for targeted intracellular production of reactive oxygen species.

Correction for 'Controlled functionalization of carbon nanodots for targeted intracellular production of reactive oxygen species' by Ding-Kun Ji et al., Nanoscale Horiz., 2020, 5, 1240-1249, DOI: .

Controlled functionalization of carbon nanodots for targeted intracellular production of reactive oxygen species.

Controlled intracellular release of exogenous reactive oxygen species (ROS) is an innovative and efficient strategy for cancer treatment. Well-designed materials, which can produce ROS in targeted cells, minimizing side effects, still need to be explored as new generation nanomedicines. Here, red-emissive carbon nanodots (CNDs) with intrinsic theranostic properties are devised, and further modified with folic acid (FA) ligand through a controlled covalent functionalization for targeted cell imaging and intracellular production of ROS. We demonstrated that covalent functionalization is an effective strategy to prevent the aggregation of the dots, leading to superior colloidal stability, enhanced luminescence and ROS generation. Indeed, the functional nanodots possess a deep-red emission and good dispersibility under physiological conditions. Importantly, they show excellent targeting properties and generation of high levels of ROS under 660 nm laser irradiation, leading to efficient cell death. These unique properties enable FA-modified carbon nanodots to act as a multifunctional nanoplatform for simultaneous targeted imaging and efficient photodynamic therapy to induce cancer cell death.

Is carboxylation an efficient method for graphene oxide functionalization?

Graphene oxide (GO) is one of the most popular materials applied in different research areas thanks to its unique properties. The application of GO requires well-designed protocols to introduce different functionalities on its surface, exploiting the oxygenated groups already present. Due to the complex and unstable chemical environment on the GO surface, it is recommended to perform the functionalization under mild conditions. The carboxylation of GO is a widely used method to introduce additional carboxylic acids, which could be further modified through amidation or esterification reactions. The strategy already reported in the literature requires harsh conditions (excess amount of sodium hydroxide). GO is readily reduced under basic conditions, but the reduction of GO during the carboxylation is barely studied. In this work, we performed the carboxylation using chloroacetic acid with different amounts of sodium hydroxide and characterized the functionalized GO with various techniques. The carboxylated GO was exploited to develop a double functionalization approach combining an epoxide ring opening reaction and an amidation. The results showed that strong basic conditions were necessary to derivatize GO. Nevertheless, these conditions resulted in a partial reduction of GO and some functionalities on GO were removed during the reaction, thus reducing the total efficiency of the functionalization in comparison to an epoxide ring opening reaction, indicating that carboxylation is not an efficient approach for the functionalization of GO.

Physically-triggered nanosystems based on two-dimensional materials for cancer theranostics.

There is an increasing demand to develop effective methods for treating malignant diseases to improve healthcare in our society. Stimuli-responsive nanosystems, which can respond to internal or external stimuli are promising in cancer therapy and diagnosis due to their functionality and versatility. As a newly emerging class of nanomaterials, two-dimensional (2D) nanomaterials have attracted huge interest in many different fields including biomedicine due to their unique physical and chemical properties. In the past decade, stimuli-responsive nanosystems based on 2D nanomaterials have been widely studied, showing promising applications in cancer therapy and diagnosis, including phototherapies, magnetic therapy, drug and gene delivery, and non-invasive imaging. Here, we will focus our attention on the state-of-the-art of physically-triggered nanosystems based on graphene and two-dimensional nanomaterials for cancer therapy and diagnosis. The physical triggers include light, temperature, magnetic and electric fields.

Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties.

The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide-alkyne "click" conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with Kd values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30-40% residual adhesion observed. The fluorescence properties of the PDI core were then investigated by confocal microscopy on cell-bacteria cultures. However, the red fluorescence signal of the PDI-based glycocluster was too weak to provide significant data. The present study provides another type of anti-adhesive glycocluster against bacterial infection with a large aromatic PDI core.

Supramolecular assembly of fluorogenic glyco-dots from perylenediimide-based glycoclusters for targeted imaging of cancer cells.

Supramolecular self-assembly between perylenediimide-based glycoclusters and a red-emitting fluorophore produces structurally uniform and stable glyco-dots amenable to targeted fluorogenic imaging of liver and triple-negative breast cancer cells.

Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release.

The early detection and thus treatment of breast cancer bone metastasis remain a big challenge clinically. As the most abundant cells within bone tissue, osteocytes have been found to manipulate the activity of early cancer bone metastasis by its crosstalk with cancer cells and osteoclasts. However, conventional bone-targeting nanomedicine has limited bone-lesion specificity and ignores the vital role of osteocytes during breast cancer bone metastasis. Also, it lacks detailed insight into the therapeutic mechanisms, which hinders the following translational practice. Previously, we have shown that a combination of zoledronic acid (ZA) and plumbagin (PL) synergistically alleviates cancer-induced bone destruction. Herein, we further develop a pH-responsive bone-targeting drug delivery system, i.e., the ZA-anchored bimodal mesoporous slica covered gadolinium(III) upconversion nanoparticles loaded with PL, to detect and treat bone metastasis sensitively and specifically at an early stage. This multifunctional nanosystem can target osteocytes to release PL as controlled by pH, decreasing osteocytic RANKL expression synergistically through the structural simulation of adenosine phosphate, which competitively inhibits the phosphorylation of osteocytic protein kinase-a, cAMP-response element binding protein, extracellular regulated protein kinase, and c-Jun N-terminal kinase. More importantly, by establishing a breast cancer bone metastasis mice model via intracardiac injection, we show that tumoriogenesis and osteoclastogenesis can both be attenuated significantly. We thereby realize the effective theranostics of tiny bone metastasis in breast cancer bone metastasis. Our work highlights the significance of theranostic nanomedicine and osteocyte-targeting therapy in the treatment of early bone metastasis, which could be applied in achieving efficient theranostic effects for other bone diseases.

Targeted Intracellular Production of Reactive Oxygen Species by a 2D Molybdenum Disulfide Glycosheet.

A 2D "glycosheet" based on supramolecular self-assembly between 2D MoS2 and fluorescent glycoligands is developed. The composite 2D material is proven suitable for targeted intracellular production of reactive oxygen species (singlet oxygen) by the sequential control of a receptor endocytosis and light irradiation.

Targeted fluorescence imaging enhanced by 2D materials: a comparison between 2D MoS2 and graphene oxide.

Here we demonstrate that 2D MoS2 can enhance the receptor-targeting and imaging ability of a fluorophore-labelled ligand. The 2D MoS2 has an enhanced working concentration range when compared with graphene oxide, resulting in the improved imaging of both cell and tissue samples.