Bio-based fluorescent carbon dots (CDs) have emerged as promising material for advanced sensing applications due to their exceptional sensitivity, stability and biocompatibility. However, it was till constrained by ion selectivity and solution suitability especially in physiological solutions (e.g., PBS). Herein, a novel nitrogen-doped carbon dots (N-CDs) fluorescence quenching sensor derived from Siraitia grosvenorii (named “Luo Han Guo” in China) residue was developed for selective determination of trace Cu(II) ions in different solutions. The N-CDs were synthesized through a one-step hydrothermal process utilizing agricultural waste as carbon precursor and urea as the nitrogen source, demonstrating an eco-friendly synthesis strategy. The developed sensor exhibited remarkable anti-interference capability against acid, base, salt and various metal ions while maintaining excellent photostability and biocompatibility (cell viability > 75
IntroductionAntimony (Sb) has been used as a medication for centuries, while it has rarely been investigated in plasmonic phototherapy, partly due to the lack of effective liquid-phase controllable synthesis methods to construct Sb nanocrystals with an optimized absorption curve within the biological transparent window (near-infrared region), achieving more effective and less side-effect phototherapy.MethodsHerein, an effective ligand-guided growth strategy was employed to synthesize Sb nanoparticles (Sb NPs) with high photothermal conversion efficiency (PTCE). The spatial electric field distribution of Sb NPs was simulated by the finite-difference time-domain (FDTD) method to validate their localized surface plasmon resonance (LSPR) effect. Sb NPs were coated with polydopamine (PDA) and polyethylene glycol (PEG) to enhance their biocompatibility. The synergistic anti-hepatoma activities of Sb NPs were evaluated via in vitro experiments.ResultsSb NPs were successfully obtained via a ligand-guided growth strategy. Uv-vis absorption peak was observed to red-shift from 520 nm to 810 nm as the size of Sb NPs increased from 40 nm to 70 nm. Sb NPs achieve a PTCE of 59.3% under 808 nm resonant excitation and was favorable to photothermal therapy (PTT). Sb NPs also exhibit 660 nm laser responsiveness, producing reactive oxygen species (ROS) that enable photodynamic therapy (PDT). In vitro anti-BEL-7404 hepatoma cells experiments revealed that 660 nm/808 nm laser irradiation could inhibit proliferation, promote apoptosis, and induce G2/M phase blockage tendency, with combined irradiation exhibiting more significant effects.ConclusionThe fabricated Sb-PDA exhibits synergistic PTT/PDT potential, though its in vivo efficacy and mechanisms warrant deeper investigation. LSPR-induced Sb-based nanomedicine may unlock diverse biomedical applications of semimetals.
Chronic prostatitis (CP) is one of the general diseases in urological practice, with category III prostatitis being particularly prevalent. The trace metal abnormalities might be a primary cause of prostatitis, however, their specific roles in category III prostatitis remain largely unexplored. In total, 42 expressed prostatic secretion (EPS) samples from IIIa prostatitis patients, 42 from IIIb prostatitis patients, and 45 from controls were collected, along with 42 serum samples from IIIa prostatitis patients, 45 from IIIb prostatitis patients, and 50 from controls for analysis in this study. To investigate the diagnostic potential of trace metals in category III prostatitis, we analyzed the concentration of zinc (Zn), copper (Cu), calcium (Ca) and magnesium (Mg) in EPS and serum of patients with category III prostatitis and healthy controls using a flame atomic absorption spectrometer (FAAS). The Results showed that the concentrations of Zn, Ca and Mg in both serum and EPS samples of all subjects with category III prostatitis were significantly different compared to controls (all P < 0.05), while Cu levels were significantly altered in all EPS samples (P < 0.000). In the category of IIIa prostatitis group, the levels of Zn, Ca, Mg in EPS, as well as Ca in serum were significantly reduced (all P < 0.000), whereas the serum Zn level was markedly elevated (P < 0.000). In the category IIIb prostatitis group, the EPS levels of Zn, Ca, Mg were decreased significantly (all P < 0.05), and the levels of serum Ca, Mg were markedly decreased (all P < 0.000), however, the EPS Cu level increased significantly (P < 0.05). Moreover, receiver operating characteristic (ROC) analysis showed that the levels of Mg and Zn/Mg in EPS had better diagnostic value for category IIIa prostatitis (Area Under the ROC Curve(AUC) = 0.796, 0.791, respectively, all P < 0.0001); while Cu and Cu/Ca levels exhibited better diagnostic value for category IIIb prostatitis (AUC = 0.880, 0.901, respectively, all P < 0.0001). Summarily, there are significant abnormalities in the concentrations of Cu, Mg, Ca, and Zn in EPS and serum samples of patients with category III prostatitis. The levels of Mg, Cu, Zn/Mg, Cu/Ca in EPS may serve as potential diagnostic markers for category III prostatitis.
Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.
Protective autophagy can be activated by external stimuli such as chemotherapy (CT) and photothermal therapy (PTT), leading to tumour resistance. As a key subcellular for autophagy, lysosomal dysfunction is crucial for autophagy suppression. Furthermore, lysosomal drug sequestration enhances basic drug resistance such as doxorubicin (DOX), which is trapped away from its target site, namely, the nucleus. Moreover, most of nanodrug delivery systems are internalised to lysosome for degradation, which further leads to DOX resistance. Lysosome serves as an essential organelle in drug resistance mechanisms, whose acidification arrest provides a potential strategy to inhibit autophagy and lysosomal drug sequestration simultaneously. The chloride channel-3 (ClC-3) protein is known as an important Cl--H+ transporter to maintain lysosomal pH at low values of various human cells. Herein, a black phosphorus-based theranostic nanoplatform of BP-A-S@D is constructed, and HeLa cells are used as a model to verify the effect of ClC-3 on tumour lysosomal acidification and autophagy regulation. Consequently, ClC-3 silencing inhibits not only protective autophagy to sensitise chemo-photothermal therapy, but also DOX resistance by suppressing lysosomal acidification. Therefore, ClC-3 silencing could simultaneously inhibit autophagy and lysosomal drug sequestration to improve anti-tumour efficiency.
Background: Rechargeable aqueous zinc-ion batteries are considered sustainable energy storage systems due to low cost and inherent safety. Rational design of cathode materials for reliable energy storage receives great interest to the research field. Methods: This work reveals advanced Cu-intercalated MnO2 (CMO) cathode can be obtained through an ion exchange treatment. Ex situ XPS, TEM, and XRD analyses are used to reveal the charge storage mechanism of CMO. Significant findings: CMO with highly porous morphology boosts ion transport kinetics and shows better utilization of electrolyte Mn2+. The ion diffusion coefficient in CMO is much higher than pristine MnO2 (MO) by a factor of similar to 10 times. Moreover, CMO undergoes displacement mechanism forming metallic Cu during battery operation, leading to improved electronic conductivity. As a result, CMO exhibits promising electrochemical performance with higher capacity (236 vs. 156 mAh g(-1) at 0.5 A g(-1)), better rate performance (95 vs. 61 mAh g(-1) at 8 A g(-1)), improved electrochemical reversibility (0.26 vs 0.48 Vat 1.5 mV s(-1)), higher energy efficiency (83.7 vs. 79.0 % at 8 A g(-1)), reduced charge-transfer resistance (45 vs. 212 Omega), and enhanced energy storage (322.7 vs. 214.4 Wh kg(-1) at 0.5 A g(-1)) in comparison with the MO counterpart. (C) 2021 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
Light-sensitive nanomaterial-released thermia is an emerging approach for cancer therapy. However, the therapeutic efficacy of this approach is generally modest and several challenging issues remain unresolved, including ineffective conversion from light to heat production, uncontrolled release of anticancer drugs, and non-specific delivery of nanomaterials to the tumor site. Here, we propose a new therapeutic concept by converting a photothermal nanomaterial to tumor cell-killing gas in the tumor microenvironment (TME) for gasothermal therapy. This novel strategy employed a chemical coordination (BPN-MnCO) between light-sensitive black phosphorous nanomaterial (BPN) and metal carbonyl (MnCO). The absorption of near-infrared red (NIR) light by BPN triggered the photochemical degradation of coordinated MnCO to produce a high concentration of carbon monoxide (CO) as well as hyperpyrexia in the local TME. Additionally, the surface coordination of MnCO protected BPN from biodegradation to achieve a long-lasting effect of heat production, which went through a feedback mechanism to effectively produce anticancer CO. In various preclinical cancer models, we showed that this approach nearly completely eradicated tumors without causing any notable adverse effects. Mechanistically, we discovered that BPN-generated heat inhibited the repair process of the CO-induced DNA damage and thus accelerated the ATM–GADD45–P53–Cyclin B cell death signaling. In summary, we provide compelling experimental evidence to support our new concept of gasothermal anticancer therapy that is likely to shift a new paradigm for effective treatment of cancer.
Most anticancer drugs with broad toxicities are systematically administrated to cancer patients and their distribution in tumors is extremely low owing to hypoxia, which compromises the therapeutic efficacies of these cancer drugs. Consequently, a preponderant proportion of cancer drugs is distributed in off‐target‐healthy tissues, which often causes severe adverse effects. Precision cancer therapy without overdosing patients with drugs remains one of the most challenging issues in cancer therapy. Here, a novel concept of nanopoxia is presented, which is a tumor‐hypoxia‐based photodynamic nanoplatform for the release of therapeutic agents to achieve precision cancer therapy. Under tumor hypoxia, exposure of tumors to laser irradiation induces the fracture of polymer outer shell and produces anticancer reactive oxygen species, and switches 2D antimonene (Sb) nanomaterials to cytotoxic trivalent antimony to synergistically kill tumors. In preclinical cancer models, delivery of Sb nanomaterials to mice virtually ablates tumor growth without producing any detectable adverse effects. Mechanistically, the tumor hypoxia‐triggered generation of trivalent antimony displays direct damaging effects on cancer cells and suppression of tumor angiogenesis. Together, the study provides a proof‐of‐concept of hypoxia‐based precision cancer therapy by developing a novel nanoplatform that offers multifarious mechanisms of cancer eradication.
Rechargeable aqueous zinc−ion batteries (ZIBs) with cost−effective and environmentally friendly characteristics show great potential for large−scale energy storage systems. Among all cathode material candidates, layered vanadates are promising owing to their suitable open structure for accommodating Zn2+/H+. However, the unsatisfactory rate capability and cycling stability of vanadate cathodes have hindered the practical application. Thus, the exploration of high−performance and structural stable cathode materials is urgently needed. In this study, a La0.14V2O5/reduced graphene oxide composite material (denoted as LaVO/rGO) can be successfully synthesized by a facile hydrothermal procedure. With the pillar La3+ ions and highly conductive rGO, the layered LaVO/rGO has the merits of large interlayer distance (14.7 A), low charge transfer resistance, and high diffusion coefficient that guarantee fast kinetics of Zn2+/H+ intercalation/de−intercalation. As a result, the LaVO/rGO cathode delivers a high−rate performance which obtains high capacity of 298 mAh g−1 at 0.3 A g−1. Even up to 8 A g−1, high capacity of 166 mAh g−1 can be achieved. Stable cycle performance with the capacity retention of 88% over 6000 cycles is attained, benefiting from fast and reversible Zn2+/H+ storage in the host material.
As one of the main elements in the living organisms, phosphorus makes an important impact on the life activity. Phosphorus contained compounds have been widely applied in the biomedical field. As nanotechnology develops, a variety of phosphorus-based nanomaterials have also been developed for the biomedical application. The recently discovered superior biological property of two-dimensional black phosphorus (2D BP), i.e. phosphorene, including low toxicity and biodegradability, makes it especially outstanding, such as biosensors for the disease diagnosis. Upon light or ultrasound irradiation on the phosphorene, reactive oxygen species (ROS) or heat can be generated for the disease therapy. Moreover, phosphorene can smartly and efficiently deliver drugs. Thus, it is suitable in many single or combined therapy modalities. This short article reviews the progress from phosphorus to phosphorene to be used as biomedical materials, especially the phosphorene as the biosensor and sensitizer for the disease diagnosis and therapy, including the tumor, the neurodegenerative disease, the bone disease and other diseases. The challenges and prospective of the phosphorene for the biomedical applications are also discussed. (C) 2021 Elsevier B.V. All rights reserved.
Aqueous zinc-ion batteries are considered promising next-generation systems for large-scale energy storage due to low cost, environmental friendliness, and high reversibility of the Zn anode. However, the interfacial charge-transfer resistance for the insertion of divalent Zn2+ into cathode materials is normally high, which limits the kinetics of Zn2+ transfer at the cathode/electrolyte interface. This study reveals the presence of rich structural water in spinel ZnMn2O4 (ZnMn2O4·0.94H2O, denoted as ZMO), synthesized by a scalable and low-temperature process, significantly overcoming the great interfacial charge-transfer resistance. ZMO exhibits excellent electrochemical performance toward Zn storage, that is, high capacity (230 and 101 mA h g-1 at 0.5 and 8 A g-1), high specific energy/specific power (329 W h kg-1/706 W kg-1 and 134 W h kg-1/11,160 W kg-1), and stable cycle retention (75% after 2000 cycles at 4 A g-1) can be achieved. On the contrary, the controlled sample ZMO-450 with deficient structural water, prepared by post-heat treatment of ZMO at 450 °C, demonstrates limited discharge capacity (45 and 15 mA h g-1 at 0.5 and 8 A g-1). As examined by electrochemical impedance spectroscopy, rich structural water in ZMO effectively reduces the activation energy barrier upon Zn2+ insertion, rendering fast interfacial kinetics for Zn storage. Benefiting from rich structural water in ZMO, the involvement of Zn2+ during the charge/discharge process exhibits good reversibility, as characterized by X-ray diffraction and X-ray photoelectron spectroscopy.
Ischemic stroke is still a serious threat to human life and health, but there are few therapeutic options available to treat stroke because of limited blood-brain penetration. The development of nanotechnology may overcome some of the problems related to traditional drug development. In this review, we focus on the potential applications of nanotechnology in stroke. First, we will discuss the main molecular pathological mechanisms of ischemic stroke to develop a targeted strategy. Second, considering the important role of the blood-brain barrier in stroke treatment, we also delve mechanisms by which the blood-brain barrier protects the brain, and the reasons why the therapeutics must pass through the blood-brain barrier to achieve efficacy. Lastly, we provide a comprehensive review related to the application of nanomaterials to treat stroke, including liposomes, polymers, metal nanoparticles, carbon nanotubes, graphene, black phosphorus, hydmgels and dendrimers. To conclude, we will summarize the challenges and future prospects of nanomedicine-based stroke treatments.
Nanoparticulate chemotherapeutics hold great potential for inducing reactive oxygen species (ROS) overproduction and exerting antihypoxic effects for efficient cancer radiotherapy. However, previous strategies for designing smart radiosensitizers necessitate the multistep incorporation of nanomaterials to achieve valuable radiosensitive outcomes, which causes unpredictable safety issues including poor decomposition and undefined biotransformations. Ultrathin antimonene nanoparticles (AMNPs) are demonstrated as new radiosensitizers that achieve an efficient radiochemotherapeutic effect through the induction of a strong oxidative stress response and their significantly high radiotoxicity in vivo. Analyzing the irradiation process of AMNPs indicates that irradiation accelerates photoelectron generation and the valence transition to toxic Sb2O3, leading to cancer cell apoptosis and S-phase arrest. The tumor regression activity and concealed biotoxicity of the AMNPs in a melanoma mouse model enhance the applicability of antimonene to overcoming radioresistance by increasing ROS generation and normoxia. This new technology can extend the applications of antimonene as an effective radiosensitizer and can promote its clinical translation for tunable and effective radiosensitization in the future.
Black phosphorus (BP), an emerging 2D material semiconductor material, exhibits unique properties and promising application prospects for photo/electrocatalysis. However, the applications of BP in photo/electrocatalysis are hampered by the instability as well as low catalysis efficiency. Recently, tremendous efforts have been dedicated toward modulating its intrinsic structure, electronic property, and charge separation for enhanced photo/electrocatalytic performance through structure engineering. Simultaneously, the search for new substitute materials that are BP-analogous is ongoing. Herein, the latest theoretical and experimental progress made in the structural/surface engineering strategies and advanced applications of BP and BP-analog materials in relation to photo/electrocatalysis are extensively explored, and a presentation of the future opportunities and challenges of the materials is included at the end.
The circulating tumor cell (CTC) count is closely related to cancer recurrence and metastasis. The technology that can in vivo destroy CTCs may bring great benefits to patients, which is an urgent clinical demand. Here, a minimally invasive therapeutic intravenous catheter for in vivo enriching and photothermal killing of CTCs is developed. The surface of catheter is modified with anti-EpCAM antibody and the interior is filled with black phosphorus nanosheets (BPNSs). CTCs in the peripheral blood are captured by the catheter continually with the aid of circulation. The captured CTCs are used for downstream analyses or in vivo eliminated by the near-infrared (NIR) photothermal effect of BPNSs. A capture efficiency of 2.1% is obtained during the 5 min of treatment, and 100% of the captured CTCs are killed by following NIR light irradiation in both an in vitro closed-loop circulation system and an in vivo rabbit model. This cost-effective modality for lowering the CTCs burden can be a good supplement to traditional therapies, which holds great promise as an effective clinical intervention for cancer patients.
Bismuthene, a monoelemental two-dimensional material, has shown promise in the biomedical, electronic, and energy fields due to its high carrier mobility and stability at room temperature. However, its use in biosensing applications is restricted due to its undefined quenching mechanism for dye molecules. Herein, we developed a novel ultrathin bismuthene-based sensing platform for microRNA (miRNA)-specific detection that even discriminates single-base mismatches. The detection limit can reach 60 pM. Excitingly, with the fluorescence quenching mechanism of bismuthene, ground state weakly fluorescent charge transfer is determined via femtosecond pump-probe spectroscopy. This finding provides a proof-of-concept platform to (i) fundamentally explore the quenching mechanism of bismuthene and (ii) sensitively detect miRNA molecules for early cancer.
Since the successful fabrication of two-dimensional (2D) tellurium (Te) in 2017, its fascinating properties including a thickness dependence bandgap, environmental stability, piezoelectric effect, high carrier mobility, and photoresponse among others show great potential for various applications. These include photodetectors, field-effect transistors, piezoelectric devices, modulators, and energy harvesting devices. However, as a new member of the 2D material family, much less known is about 2D Te compared to other 2D materials. Motivated by this lack of knowledge, we review the recent progress of research into 2D Te nanoflakes. Firstly, we introduce the background and motivation of this review. Then, the crystal structures and synthesis methods are presented, followed by an introduction to their physical properties and applications. Finally, the challenges and further development directions are summarized. We believe that milestone investigations of 2D Te nanoflakes will emerge soon, which will bring about great industrial revelations in 2D materials-based nanodevice commercialization.
During photothermal therapy (PTT), hyperthermia up to 50 degrees C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep-seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2 alpha-dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor-specific delivery and near-infrared (NIR) light-controlled release of the SG inhibitor Emetine. Upon NIR-light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light-controlled release of Emetine in tumor tissues effectively inhibits PTT-induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT.
Here, we describe a combination strategy of black phosphorus (BP)-based photothermal therapy together with anti-CD47 antibody (aCD47)-based immunotherapy to synergistically enhance cancer treatment. Tumour resistance to immune checkpoint blockades in most cancers due to immune escape from host surveillance, along with the initiation of metastasis through immunosuppressive cells in the tumour microenvironment, remains a significant challenge for cancer immunotherapy. aCD47, an agent for CD47/SIRPα axis blockade, induces modest phagocytic activity and a low response rate for monotherapy, resulting in failures in clinical trials. We showed that BP-mediated ablation of tumours through photothermal effects could serve as an effective strategy for specific immunological stimulation, improving the inherently poor immunogenicity of tumours, which is particularly useful for enhancing cancer immunotherapy. BP in combination with aCD47 blockade activates both innate and adaptive immunities and promotes local and systemic anticancer immune responses, thus offering a synergistically enhanced effect in suppression of tumour progression and in inducing abscopal effects for inhibition of metastatic cancers. Our combination strategy provides a promising platform in which photothermal agents could help to enhance the therapeutic efficacy of immunotherapy.