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A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.
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Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/efectos de la radiación , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/instrumentación , Humanos , Hidrogeles/química , Hidrogeles/efectos de la radiación , Rayos Infrarrojos , Ratones , Ratones Desnudos , Nanoestructuras/química , Fósforo/químicaRESUMEN
Black phosphorus (BP)-based nanomaterials have distinguished advantages and potential applications in various biomedical fields. However, their biological effects in physiological systems remain largely unexplored. Here, we systematically revealed a reactive oxygen species (ROS)-mediated mechanism for the selective killing of cancer cells by BP-based nanosheets. The treatment with BP-based materials can induce higher levels of ROS in cancer cells than in normal cells, leading to significant changes in the cytoskeleton, cell cycle arrest, DNA damage, and apoptosis in tumor cell lines. We revealed that the decreased superoxide dismutase activity by lipid peroxides could be an essential mechanism of the selectively higher ROS generation induced by BP-based nanosheets in cancer cells. In addition, the selective killing effect only occurred within a certain dosage range (named "SK range" in this study). Once exceeding the SK range, BP-based materials could also induce a high ROS production in normal tissues, leading to detectable DNA damage and pathological characteristics in normal organs and raising safety concerns. These findings not only shed light on a new mechanism for the selective killing of cancer cells by BP-based materials but also provide deep insights into the safe use of BP-based therapies.
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Daño del ADN , Fósforo/farmacología , Especies Reactivas de Oxígeno/química , Línea Celular Tumoral , HumanosRESUMEN
Two dimensional Bi nanosheets have been employed to fabricate electrodes for broadband photo-detection. A series of characterization techniques including scanning electron microscopy and high-resolution transmission electron microscopy have verified that Bi nanosheets with intact lamellar structure have been obtained after facile liquid phase exfoliation. In the meanwhile, UV-vis and Raman spectra are also carried out and the inherent optical and physical properties of Bi nanosheets are confirmed. Inherited from the topological characteristics of Bi bulk counterpart, the resultant Bi nanosheet-based photo-detector exhibits preferable photo-response activity as well as environmental robustness. We then evaluate the photo-electrochemical (PEC) performance of the photodetector in 1 M NaOH and 0.5 M Na2SO4 electrolytes, and demonstrated that the as-prepared Bi nanosheets may possess a great potential as PEC-type photo-detector. Additional PEC measurements show that the current density of Bi nanosheets can reach up to 830 nA cm-2, while an enhanced responsivity (1.8 µA W-1) had been achieved. We anticipate that this contribution can provide feasibility towards the construction of high-performance elemental Bi nanosheets-based optoelectronic devices in the future.
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Phosphorene has attracted great interest due to its unique electronic and optoelectronic properties owing to its tunable direct and moderate band-gap in association with high carrier mobility. However, its intrinsic instability in air seriously hinders its practical applications, and problems of technical complexity and in-process degradation exist in currently proposed stabilization strategies. A facile pathway in obtaining and stabilizing phosphorene through a one-step, ionic liquid-assisted electrochemical exfoliation and synchronous fluorination process is reported in this study. This strategy enables fluorinated phosphorene (FP) to be discovered and large-scale, highly selective few-layer FP (3-6 atomic layers) to be obtained. The synthesized FP is found to exhibit unique morphological and optical characteristics. Possible atomistic fluorination configurations of FP are revealed by core-level binding energy shift calculations in combination with spectroscopic measurements, and the results indicate that electrolyte concentration significantly modulates the fluorination configurations. Furthermore, FP is found to exhibit enhanced air stability thanks to the antioxidation and antihydration effects of the introduced fluorine adatoms, and demonstrate excellent photothermal stability during a week of air exposure. These findings pave the way toward real applications of phosphorene-based nanophotonics.
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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.
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Nanopartículas , Neoplasias de la Próstata , Masculino , Humanos , Proteína X Asociada a bcl-2 , Apoptosis , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Zinc/farmacología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
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.
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Canales de Cloruro , Terapia Fototérmica , Humanos , Autofagia , Canales de Cloruro/genética , Doxorrubicina/farmacología , Doxorrubicina/metabolismo , Células HeLa , Concentración de Iones de Hidrógeno , Lisosomas/metabolismo , FototerapiaRESUMEN
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.
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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, hydrogels and dendrimers. To conclude, we will summarize the challenges and future prospects of nanomedicine-based stroke treatments.
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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.
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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.
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Técnicas Biosensibles , Bismuto/química , Fluorescencia , MicroARNs/análisis , Nanoestructuras/química , Imagen Óptica , Tamaño de la PartículaRESUMEN
Monoelemental two-dimensional (2D) materials (Xenes) aroused a tremendous attention in 2D science owing to their unique properties and extensive applications. Borophene, one emerging and typical Xene, has been regarded as a promising agent for energy, sensor, and biomedical applications. However, the production of borophene is still a challenge because bulk boron has rather intricate spatial structures and multiple chemical properties. In this review, we describe its excellent properties including the optical, electronic, metallic, semiconducting, photoacoustic, and photothermal properties. The fabrication methods of borophene are also presented including the bottom-up fabrication and the top-down fabrication. In the end, the challenges of borophene in the latest applications are presented and perspectives are discussed.
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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.
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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.
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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.
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Two-dimensional (2D) metal-free sheets with atomic thickness have been highly considered as promising candidates for fluorescent probes, due to their intriguing characteristics. In this work, 2D ultrathin boron nanosheets (B NSs) with a surface defect nanolayer can be effectively prepared by modified liquid phase exfoliation. The as-prepared ultrathin B NSs show blue fluorescence characteristics even with a quantum yield efficiency of up to 10.6%. Such luminescent behavior originates from the quantum confinement effect and the existence of a surface defect layer. In light of the advantages of being environmentally friendly, having high photostability and good biocompatibility, for the first time we have shown that ultrathin B NSs can be used as an emerging fluorescent probe for application in cellular bioimaging. It is believed that this work will open new avenues for ultrathin B NSs in biomedical fields, and it will also inspire the development of other elemental 2D nanomaterials.
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Boro/química , Colorantes Fluorescentes/química , Nanoestructuras/química , Boro/efectos de la radiación , Boro/toxicidad , Fluorescencia , Colorantes Fluorescentes/efectos de la radiación , Colorantes Fluorescentes/toxicidad , Células HeLa , Humanos , Microscopía Confocal , Microscopía Fluorescente , Nanoestructuras/efectos de la radiación , Nanoestructuras/toxicidad , Rayos UltravioletaRESUMEN
MicroRNA exhibits differential expression levels in cancer and can affect cellular transformation, carcinogenesis and metastasis. Although fluorescence techniques using dye molecule labels have been studied, label-free molecular-level quantification of miRNA is extremely challenging. We developed a surface plasmon resonance sensor based on two-dimensional nanomaterial of antimonene for the specific label-free detection of clinically relevant biomarkers such as miRNA-21 and miRNA-155. First-principles energetic calculations reveal that antimonene has substantially stronger interaction with ssDNA than the graphene that has been previously used in DNA molecule sensing, due to thanking for more delocalized 5s/5p orbitals in antimonene. The detection limit can reach 10 aM, which is 2.3-10,000 times higher than those of existing miRNA sensors. The combination of not-attempted-before exotic sensing material and SPR architecture represents an approach to unlocking the ultrasensitive detection of miRNA and DNA and provides a promising avenue for the early diagnosis, staging, and monitoring of cancer.