Metal Cation‐Assisted Synthesis of Amorphous B,N Co‐Doped Carbon Nanotubes for Superior Sodium Storage

Nearly inexhaustible sodium sources on earth make sodium ion batteries (SIBs) the best candidate for large‐scale energy storage. However, the main obstacles faced by SIBs are the low rate performance and poor cycle stability caused by the large size of Na⁺ ions. Herein, a universal strategy for synthesizing amorphous metals encapsulated into amorphous B, N co‐doped carbon (a‐M@a‐BCN; M = Co, Ni, Mn) nanotubes by metal cation‐assisted carbonization is explored. The methodology allows tailoring the structures (e.g., length, wall thickness, and metals doping) of a‐M@a‐BCN nannotubes at the molecular level. Furthermore, the amorphous metal sulfide encapsulated into a‐BCN (a‐MS_x@a‐BCN; MS_x: CoS, Ni₃S₂, MnS) nanotubes are obtained by one‐step sulfidation process. The a‐M@a‐BCN and a‐MS_x@a‐BCN possess the larger interlayer spacing (0.40 nm) amorphous carbon nanotube rich in heteroatoms active sites, making them exhibit excellent Na⁺ ions diffusion kinetics and capacitive storage behavior. As SIBs anodes, they show high capacity, excellent rate performance, and long cycle stability.     

Addressable Peptide Self‐Assembly on the Cancer Cell Membrane for Sensitizing Chemotherapy of Renal Cell Carcinoma

Chemotherapy has been validated unavailable for treatment of renal cell carcinoma (RCC) in clinic due to its intrinsic drug resistance. Sensitization of chemo‐drug response plays a crucial role in RCC treatment and increase of patient survival. Herein, a recognition‐reaction‐aggregation (RRA) cascaded strategy is utilized to in situ construct peptide‐based superstructures on the renal cancer cell membrane, enabling specifically perturbing the permeability of cell membranes and enhancing chemo‐drug sensitivity in vitro and in vivo. First, P1‐DBCO can specifically recognize renal cancer cells by targeting carbonic anhydrase IX. Subsequently, P2‐N₃ is introduced and efficiently reacts with P1‐DBCO to form a peptide P3, which exhibits enhanced hydrophobicity and simultaneously aggregates into a superstructure. Interestingly, the superstructure retains on the cell membrane and perturbs its integrity/permeability, allowing more doxorubicin (DOX) uptaken by renal cancer cells. Owing to this increased influx, the IC₅₀ is significantly reduced by nearly 3.5‐fold compared with that treated with free DOX. Finally, RRA strategy significantly inhibits the tumor growth of xenografted mice with a 3.2‐fold enhanced inhibition rate compared with that treated with free DOX. In summary, this newly developed RRA strategy will open a new avenue for chemically engineering cell membranes with diverse biomedical applications.     

Surface Nanopore Engineering of 2D MXenes for Targeted and Synergistic Multitherapies of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and deadly gastrointestinal malignancies. Given its insensitivity to traditional systematic chemotherapy, new therapeutic strategies for efficient HCCs treatment are urgently needed. Here, the development of a novel 2D MXene‐based composite nanoplatform for highly efficient and synergistic chemotherapy and photothermal hyperthermia against HCC is reported. A surface‐nanopore engineering strategy is developed for the MXenes’ surface functionalization, which achieves the uniform coating of a thin mesoporous‐silica layer onto the surface of 2D Ti₃C₂ MXene (Ti₃C₂@mMSNs). This strategy endows MXenes with well‐defined mesopores for on‐demand drug release/delivery, enhanced hydrophilicity/dispersity, and abundant surface chemistry for targeting engineering. Systematic in vitro and in vivo evaluations have demonstrated the high active‐targeting capability of arginine‐glycine‐aspartic acid (RGD)‐targeting Ti₃C₂@mMSNs into tumor, and the synergistic chemotherapy (contributed by the mesoporous shell) and photothermal hyperthermia (contributed by the Ti₃C₂ MXene core) completely eradicate the tumor without obvious reoccurrence. This work not only provides a novel strategy for efficiently combating HCC by developing MXene‐based composite nanoplatforms, but also paves a new way for extending the biomedical applications of MXenes by surface‐nanopore engineering.     

Endolysosomal‐Escape Nanovaccines through Adjuvant‐Induced Tumor Antigen Assembly for Enhanced Effector CD8+ T Cell Activation

The activation of tumor‐specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight‐forward strategy of adjuvant‐induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed. The resulting functionalizable nanovaccines are equipped with a pH (low) insertion peptide (pHLIP) to facilitate endolysosomal escape and to promote cytoplasmic localization, with the aim to enhance cross‐presentation of the antigen by dendritic cells to effectively activate CD8⁺ T cell. The results demonstrate that pHLIP‐functionalized model nanovaccine can induce endolysosomal escape and enhance CD8⁺ T cell activation both in vitro and in vivo. Furthermore, based on the adjuvant‐induced antigen assembly, nanovaccines of the clinically relevant tumor‐associated antigen NY‐ESO‐1 are generated and show excellent capacity to elicit NY‐ESO‐1‐specific CD8⁺ T cell activation, demonstrating a high potential of this functionalizable nanovaccine formulation strategy for clinical applications.     

Color‐Convertible,Unimolecular, Micelle‐Based,Activatable Fluorescent Probe for Tumor‐Specific Detection and Imaging In Vitro and In Vivo

Recent years have witnessed significant progress in molecular probes for cancer diagnosis. However, the conventional molecular probes are designed to be “always‐on” by attachment of tumor‐targeting ligands, which limits their abilities to diagnose tumors universally due to the variations of targeting efficiency and complex environment in different cancers. Here, it is proposed that a color‐convertible, activatable probe is responding to a universal tumor microenvironment for tumor‐specific diagnosis without targeting ligands. Based on the significant hallmark of up‐regulated hydrogen peroxide (H₂O₂) in various tumors, a novel unimolecular micelle constructed by boronate coupling of a hydrophobic hyperbranched poly(fluorene‐co‐2,1,3‐benzothiadiazole) core and many hydrophilic poly(ethylene glycol) arms is built as an H₂O₂‐activatable fluorescent nanoprobe to delineate tumors from normal tissues through an aggregation‐enhanced fluorescence resonance energy transfer strategy. This color‐convertible, activatable nanoprobe is obviously blue‐fluorescent in various normal cells, but becomes highly green‐emissive in various cancer cells. After intravenous injection to tumor‐bearing mice, green fluorescent signals are only detected in tumor tissue. These observations are further confirmed by direct in vivo and ex vivo tumor imaging and immunofluorescence analysis. Such a facile and simple methodology without targeting ligands for tumor‐specific detection and imaging is worthwhile to further development.     

A Transformable Chimeric Peptide for Cell Encapsulation to Overcome Multidrug Resistance

Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P‐glycoprotein (P‐gp)‐mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self‐assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C₁₆‐K(TPE)‐GGGH‐GFLGK‐PEG₈, denoted as CTGP) with cathepsin B‐responsive and cell membrane‐targeting abilities can self‐assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX). After the cleavage of the Gly‐Phe‐Leu‐Gly (GFLG) sequence by pericellular overexpressed cathepsin B, CTGP@DOX is dissociated and transformed from spherical nanoparticles to nanofibers due to the hydrophilic–hydrophobic conversion and hydrogen bonding interactions. Thus obtained nanofibers with cell membrane‐targeting 16‐carbon alkyl chains can adhere firmly to the cell membrane for cell encapsulation and restricting DOX efflux. In comparison to free DOX, 45‐time higher drug retention and 49‐fold greater anti‐MDR ability of CTGP@DOX to drug‐resistant MCF‐7R cells are achieved. This novel strategy to encapsulate cells and reverse tumor MDR via morphology transformation would open a new avenue towards chemotherapy of tumor.     

In Vivo MR Imaging of Glioma Recruitment of Adoptive T‐Cells Labeled with NaGdF4‐TAT Nanoprobes

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T‐cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T‐cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T‐cell immunotherapy targeting glioma. In this work, ultrasmall T₁ MR‐based nanoprobes, NaGdF₄‐TAT, as molecular probes with high longitudinal relaxivity (8.93 mm ^?1 s^?1) are designed. By means of HIV‐1 transactivator (TAT) peptides, nearly 95% of the adoptive T‐cells are labeled with the NaGdF₄‐TAT nanoprobes without any measurable side effects on the labeled T‐cells, which is remarkably superior to that of the control fluorescein isothiocyanate‐NaGdF₄ concerning labeling efficacy. Labeled adoptive T‐cell clusters can be sensitively tracked in an orthotopic GL261‐glioma model 24 h after intravenous infusion of 10⁷ labeled T‐cells by T₁‐weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF₄‐TAT nanoprobes labeling of T‐cells may be a promising method to track adoptive T‐cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.     

Mechanical properties and bonding structure of boron carbon nitride films synthesized by dual ion beam sputtering

The BCN films were synthesized on Si (110) wafers by using dual ion beam sputtering deposition from boron carbide target. The influences of ion assist source energy and N₂ relative flow rate on the surface roughness, mechanical properties and chemical bonding structure of BCN films were investigated systematically. The surface roughness was measured using non-contact optical surface profilometer and the mechanical properties of BCN films were evaluated with nano-indenter. The BCN films were characterized by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS), respectively. The results showed that the BCN films' surface roughness varied in the range of 5–15 nm, and their hardness and reduced elastic modulus fluctuated in the scope of 18–29 GPa and 192–229 GPa, respectively. When the BCN films' surface roughness varied in the range of 8–12 nm, the values of hardness and reduced elastic modulus were fluctuated slightly. The BCN films with the smoothest surface (R_a = 5 nm) and the highest hardness of 28 GPa were obtained at the ion assist source energy of 200 eV and the N₂ relative flow rate of 50%. The BCN films were amorphous and contained several bonding states such as B–N, B–C and C–N with B–C–N hybridization.     

Somatostatin Receptor‐Mediated Tumor‐Targeting Nanocarriers Based on Octreotide‐PEG Conjugated Nanographene Oxide for Combined Chemo and Photothermal Therapy

Nano‐sized in vivo active targeting drug delivery systems have been developed to a high anti‐tumor efficacy strategy against certain cancer‐cells‐specific. Graphene based nanocarriers with unique physical and chemical properties have shown significant potentials in this aspect. Here, octreotide (OCT), an efficient biotarget molecule, is conjugated to PEGylated nanographene oxide (NGO) drug carriers for the first time. The obtained NGO‐PEG‐OCT complex shows low toxicity and excellent stability in vivo and is able to achieve somatostatin receptor‐mediated tumor‐specific targeting delivery. Owing to the high loading efficiency and accurate targeting delivery of anti‐cancer drug doxorubicin (DOX), our DOX loaded NGO‐PEG‐OCT complex offers a remarkably improved cancer‐cell‐specific cellular uptake, chemo‐cytotoxicity, and decreased systemic toxicity compared to free DOX or NGO‐PEG. More importantly, due to its strong near‐infrared absorption, the NGO‐PEG‐OCT complex further enhances efficient photothermal ablation of tumors, delivering combined chemo and photothermal therapeutic effect against cancer cells.     

Artificial Engineered Natural Killer Cells Combined with Antiheat Endurance as a Powerful Strategy for Enhancing Photothermal‐Immunotherapy Efficiency of Solid Tumors

Although photothermal therapy (PTT) is preclinically applied in solid tumor treatment, incomplete tumor removal of PTT and heat endurance of tumor cells induces significant tumor relapse after treatment, therefore lowering the therapeutic efficiency of PTT. Herein, a programmable therapeutic strategy that integrates photothermal therapeutic agents (PTAs), DNAzymes, and artificial engineered natural killer (A‐NK) cells for immunotherapy of hepatocellular carcinoma (HCC) is designed. The novel PTAs, termed as Mn‐CONASHs, with 2D structure are synthesized by the coordination of tetrahydroxyanthraquinone and Mn²⁺ ions. By further adsorbing polyetherimide/DNAzymes on the surface, the DNAzymes@Mn‐CONASHs exhibit excellent light‐to‐heat conversion ability, tumor microenvironment enhanced T₁‐MRI guiding ability, and antiheat endurance ability. Furthermore, the artificial engineered NK cells with HCC specific targeting TLS11a‐aptamer decoration are constructed for specifically eliminating any possible residual tumor cells after PTT, to systematically enhance the therapeutic efficacy of PTT and avoid tumor relapse. Taken together, the potential of A‐NK cells combined with antiheat endurance as a powerful strategy for immuno‐enhancing photothermal therapy efficiency of solid tumors is highlighted, and the current strategy might provide promising prospects for cancer therapy.     

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy

Mitochondrial‐targeting therapy is an emerging strategy for enhanced cancer treatment. In the present study, a multistage targeting strategy using doxorubicin‐loaded magnetic composite nanoparticles is developed for enhanced efficacy of photothermal and chemical therapy. The nanoparticles with a core–shell–SS–shell architecture are composed of a core of Fe₃O₄ colloidal nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol) linked to the PDA by disulfide bonds. The magnetic core can increase the accumulation of nanoparticles at the tumor site for the first stage of tumor tissue targeting. After the nanoparticles enter the tumor cells, the second stage of mitochondrial targeting is realized as the mPEG shell is detached from the nanoparticles by redox responsiveness to expose the TPP. Using near‐infrared light irradiation at the tumor site, a photothermal effect is generated from the PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded doxorubicin can rapidly enter the mitochondria and subsequently damage the mitochondrial DNA, resulting in cell apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting the mitochondria significantly enhances the cancer treatment.     

Formation of B?N?C Coordination to Stabilize the Exposed Active Nitrogen Atoms in g‐C3N4 for Dramatically Enhanced Photocatalytic Ammonia Synthesis Performance

It is an important issue that exposed active nitrogen atoms (e.g., edge or amino N atoms) in graphitic carbon nitride (g‐C₃N₄) could participate in ammonia (NH₃) synthesis during the photocatalytic nitrogen reduction reaction (NRR). Herein, the experimental results in this work demonstrate that the exposed active N atoms in g‐C₃N₄ nanosheets can indeed be hydrogenated and contribute to NH₃ synthesis during the visible‐light photocatalytic NRR. However, these exposed N atoms can be firmly stabilized through forming B? N? C coordination by means of B‐doping in g‐C₃N₄ nanosheets (BCN) with a B‐doping content of 13.8 wt%. Moreover, the formed B? N? C coordination in g‐C₃N₄ not only effectively enhances the visible‐light harvesting and suppresses the recombination of photogenerated carriers in g‐C₃N₄, but also acts as the catalytic active site for N₂ adsorption, activation, and hydrogenation. Consequently, the as‐synthesized BCN exhibits high visible‐light‐driven photocatalytic NRR activity, affording an NH₃ yield rate of 313.9 µmol g^?1 h^?1, nearly 10 times of that for pristine g‐C₃N₄. This work would be helpful for designing and developing high‐efficiency metal‐free NRR catalysts for visible‐light‐driven photocatalytic NH₃ synthesis.     

Carbonitride Nanomaterials,Thin Films,and Solids

Binary, ternary, and quaternary carbonitride materials, such as CN_x, BCN, SiCN, SiBCN, AlBCN, are of significant industrial interest because of their light weight and multi‐functional properties, combining extreme hardness, oxidation resistance, and chemical inertness. The most exciting material in this family is carbon nitride C₃N₄ with expected ‘superdiamond’ properties. This report describes new approaches to the preparation of CN_x thin films, and nanoscale or bulk solids of C₃N₄ and BCN.     

Antibody‐Free Hydrogel with the Synergistic Effect of Cell Imprinting and Boronate Affinity: Toward the Selective Capture and Release of Undamaged Circulating Tumor Cells

The selective and highly efficient capture of circulating tumor cells (CTCs) from blood and their subsequent release without damage are very important for the early diagnosis of tumors and for understanding the mechanism of metastasis. Herein, a universal strategy is proposed for the fabrication of an antibody‐free hydrogel that has a synergistic effect by featuring microinterfaces obtained by cell imprinting and molecular recognition conferred by boronate affinity. With this artificial antibody, highly efficient capture of human hepatocarcinoma SMMC‐7721 cells is achieved: as many as 90.3 ± 1.4% (n = 3) cells are captured when 1 × 10⁵ SMMC‐7721 cells are incubated on a 4.5 cm² hydrogel, and 99% of these captured cells are subsequently released without any loss of proliferation ability. In the presence of 1000 times as many nontarget cells, namely, leukaemia Jurkat cells, the SMMC‐7721 cells can be captured with an enrichment factor as high as 13.5 ± 3.2 (n = 3), demonstrating the superior selectivity of the artificial antibody for the capture of the targeted CTCs. Most importantly, the SMMC‐7721 cells can be successfully captured even when spiked into whole blood, indicating the great promise of this approach for the further molecular characterization of CTCs.     

Engineering an Artificial T‐Cell Stimulating Matrix for Immunotherapy

T cell therapies require the removal and culture of T cells ex vivo to expand several thousand‐fold. However, these cells often lose the phenotype and cytotoxic functionality for mediating effective therapeutic responses. The extracellular matrix (ECM) has been used to preserve and augment cell phenotype; however, it has not been applied to cellular immunotherapies. Here, a hyaluronic acid (HA)‐based hydrogel is engineered to present the two stimulatory signals required for T‐cell activation—termed an artificial T‐cell stimulating matrix (aTM). It is found that biophysical properties of the aTM—stimulatory ligand density, stiffness, and ECM proteins—potentiate T cell signaling and skew phenotype of both murine and human T cells. Importantly, the combination of the ECM environment and mechanically sensitive TCR signaling from the aTM results in a rapid and robust expansion of rare, antigen‐specific CD8+ T cells. Adoptive transfer of these tumor‐specific cells significantly suppresses tumor growth and improves animal survival compared with T cells stimulated by traditional methods. Beyond immediate immunotherapeutic applications, demonstrating the environment influences the cellular therapeutic product delineates the importance of the ECM and provides a case study of how to engineer ECM‐mimetic materials for therapeutic immune stimulation in the future.     

FeIII‐Doped Two‐Dimensional C3N4 Nanofusiform: A New O2‐Evolving and Mitochondria‐Targeting Photodynamic Agent for MRI and Enhanced Antitumor Therapy

Local hypoxia in tumors, as well as the short lifetime and limited action region of ¹O₂, are undesirable impediments for photodynamic therapy (PDT), leading to a greatly reduced effectiveness. To overcome these adversities, a mitochondria‐targeting, H₂O₂‐activatable, and O₂‐evolving PDT nanoplatform is developed based on Fe^III‐doped two‐dimensional C₃N₄ nanofusiform for highly selective and efficient cancer treatment. The ultrahigh surface area of 2D nanosheets enhances the photosensitizer (PS) loading capacity and the doping of Fe^III leads to peroxidase mimetics with excellent catalytic performance towards H₂O₂ in cancer cells to generate O₂. As such tumor hypoxia can be overcome and the PDT efficacy is improved, whilst at the same time endowing the PDT theranostic agent with an effective T ₁‐weighted in vivo magnetic resonance imaging (MRI) ability. Conjugation with a mitochondria‐targeting agent could further increase the sensitivity of cancer cells to ¹O₂ by enhanced mitochondria dysfunction. In vitro and in vivo anticancer studies demonstrate an outstanding therapeutic effectiveness of the developed PDT agent, leading to almost complete destruction of mouse cervical tumor. This development offers an attractive theranostic agent for in vivo MRI and synergistic photodynamic therapy toward clinical applications.     

Tumor‐Targeting Multifunctional Rattle‐Type Theranostic Nanoparticles for MRI/NIRF Bimodal Imaging and Delivery of Hydrophobic Drugs

The development of theranostic systems capable of diagnosis, therapy, and target specificity is considerably significant for accomplishing personalized medicine. Here, a multifunctional rattle‐type nanoparticle (MRTN) as an effective biological bimodal imaging and tumor‐targeting delivery system is fabricated, and an enhanced loading ability of hydrophobic anticancer drug (paclitaxel) is also realized. The rattle structure with hydrophobic Fe₃O₄ as the inner core and mesoporous silica as the shell is obtained by one‐step templates removal process, and the size of interstitial hollow space can be easily adjusted. The Fe₃O₄ core with hydrophobic poly(tert‐butyl acrylate) (PTBA) chains on the surface is not only used as a magnetic resonance imaging (MRI) agent, but contributes to improving hydrophobic drug loading amount. Transferrin (Tf) and a near‐infrared fluorescent dye (Cy 7) are successfully modified on the surface of the nanorattle to increase the ability of near‐infrared fluorescence (NIRF) imaging and tumor‐targeting specificity. In vivo studies show the selective accumulation of MRTN in tumor tissues by Tf‐receptor‐mediated endocytosis. More importantly, paclitaxel‐loaded MRTN shows sustained release character and higher cytotoxicity than the free paclitaxel. This theranostic nanoparticle as an effective MRI/NIRF bimodal imaging probe and drug delivery system shows great potential in cancer diagnosis and therapy.     

Oxidation resistance of thin boron carbo-nitride films on Ge(100) and Ge nanowires

Chemical vapor deposition of thin (< 10 nm) films of amorphous boron carbo-nitride (BC_0.7N_0.08, or BCN) on Ge(100) and Ge nanowire (GeNW) surfaces was studied to determine the ability of BCN to prevent oxidation of Ge. X-ray photoelectron spectroscopy was used to track Ge oxidation of BCN-covered Ge(100) upon exposure to ambient, 50 °C deionized water, and a 250 °C atomic layer deposition HfO₂ process. BCN overlayers incorporate O immediately upon ambient or water exposure, but it is limited to 15% O uptake. If the BCN layer is continuous, the underlying Ge(100) surface is not oxidized despite the incorporation of O into BCN. The minimum continuous BCN film thickness that prevents Ge(100) oxidation is ~ 4 nm. Thinner films (≤ 3.2 nm) permitted Ge(100) oxidation in each of the oxidizing environments studied. GeNWs with a 5.7 nm BCN coating were resistant to oxidation for at least 5 months of ambient exposure. High resolution transmission electron microscopy images of HfO₂/BCN/Ge(100) cross-sections and BCN-coated GeNWs reveal clean, abrupt BCN-Ge(100) interfaces.