Search

Liposomal Amphotericin B, known as AmBisome®, is a life-saving antifungal product that sold $407 million in 2019. AmBisome® has a rather complex physical structure in that Amphotericin B (AmpB) forms a stable ionic complex with the lipid bilayer to maintain AmBisome®'s low toxicity and high stability in systemic circulation. Failed attempts to reproduce AmBisome®'s precise structure has resulted in faster drug release and higher toxicity both in vitro and in vivo. In this study, we established several analytical methodologies to quantify liposomal AmpB components, characterize thermal properties of the liposome, and determine particle size distribution, AmpB aggregation state, and drug release kinetics. We applied these methodologies together with in vitro hemolytic potential and antifungal activity tests to characterize multiple lots of AmBisome® and two generic products approved in India, Phosome® and Amphonex®. We also used Fungizone®, a micellar AmpB formulation, and "leaky" AmpB liposomes as negative controls. Our results showed that Phosome® and Amphonex® were both similar to AmBisome®, while Fungizone® and 'leaky" liposomes exhibited differences in both thermal properties and AmpB aggregation state, leading to faster drug release and higher toxicity. Due to the increased interest of the pharmaceutical industry in making generic AmBisome® and the lack of standard analytical methods to characterize liposomal AmpB products, the methodologies described here are valuable for the development of generic liposomal AmpB products.

Significance Metallic lithium plating on the graphite anode is a predominant cause for capacity decays during the fast charging of lithium-ion batteries. This work studies the lithium-plating phenomenon in a previously neglected thermodynamic perspective, taking into account practical temperature distributions within batteries. We show that elevated temperatures could enhance the equilibrium potential of Li 0 /Li + , making local lithium plating more thermodynamically favorable. Furthermore, lithium-plating patterns are correlated with temperature heterogeneities, confirming the preferential lithium plating at high-temperature regions due to both kinetic and thermodynamic origins. These findings provide possible explanations of the heterogeneous lithium-plating morphology, deepen the understandings on the lithium plating phenomenon, and will guide future strategies to realize the extreme fast charging of lithium-ion batteries.

Inactive components and safety hazards are two critical challenges in realizing high-energy lithium-ion batteries. Metal foil current collectors with high density are typically an integrated part of lithium-ion batteries yet deliver no capacity. Meanwhile, high-energy batteries can entail increased fire safety issues. Here we report a composite current collector design that simultaneously minimizes the ‘dead weight’ within the cell and improves fire safety. An ultralight polyimide-based current collector (9 μm thick, specific mass 1.54 mg cm−2) is prepared by sandwiching a polyimide embedded with triphenyl phosphate flame retardant between two superthin Cu layers (~500 nm). Compared to lithium-ion batteries assembled with the thinnest commercial metal foil current collectors (~6 µm), batteries equipped with our composite current collectors can realize a 16–26% improvement in specific energy and rapidly self-extinguish fires under extreme conditions such as short circuits and thermal runaway. Batteries need to be energy-dense as well as safe. Yi Cui and team develop an ultralight polyimide-based current collector with embedded fire retardants that enables lithium-ion batteries with much-enhanced safety and energy density.

Tumor targeted drug delivery system with high efficiency of tumor accumulation, cell internalization and endosomal escape was considered ideal for cancer therapy. Herein, a cleavable polyethylene glycol (PEG) and octaarginines (R8) co-modified liposome (CL-R8-LP) was developed, in which the cholesterol was used as an alternative anchor to the commonest phospholipids for the diversified development of surface modification. The in vitro hemolysis assay and bio-distribution study demonstrated that CL-R8-LP improved biocompatibility and tumor accumulation compared with the single R8 modified liposomes (R8-LP), since the strong positive charges, toxicity and non-specificity of R8 were efficiently shielded by the outer cleavable PEG. And the cellular uptake, cytotoxicity and apoptosis of CL-R8-LP on C26 cells were much stronger than that of control liposomes in which R8 was not included or exposed. In addition, it was confirmed that CL-R8-LP entered cells via clathrin-mediated endocytosis and the macropinocytosis, and followed by a more efficient endosomal escape compared with R8-LP due to the topology change of R8. The enhanced in vivo delivery efficiency and anti-tumor efficacy were validated in C26 bearing mice. In conclusion, the results demonstrated that CL-R8-LP was a promising vehicle for enhancing the chemotherapy of solid cancers.

The complexation and decomplexation of CO2 with a series of quinones of different basicity during electrochemical cycling in dimethylformamide solutions were studied systematically by cyclic voltammetry. In the absence of CO2, all quinones exhibited two well-separated reduction waves. For weakly complexing quinones, a positive shift in the second reduction wave was observed in the presence of CO2, corresponding to the dianion quinone-CO2 complex formation. The peak position and peak height of the first re-duction wave were unchanged, indicating no formation of complexes between the semiquinones and CO2. The relative heights of both reduction waves remained constant. In the case of strongly complexing quinones, the second reduction wave disappeared while the peak height of the first reduction wave approximately doubled, indicating that the two electrons transferred simultaneously at this potential. The observed voltammograms were rationalized through several equilibrium arguments. Both weakly and strongly complexing quinones underwent either stepwise or concerted mechanisms of oxidation and CO2 dissociation depending on the sweep rate in the cyclic voltammetric experiments. Relative to stepwise oxidation, the concerted process requires a more positive electrode potential to remove the electron from the carbonate complexes to release CO2 and regenerate the quinone. For weakly complexing quinones, the stepwise process corresponds to oxidation of the uncomplexed dianion and accompanying equilibrium shift, while for strongly complexing quinones the stepwise process would correspond to the oxidation of mono(carbonate) dianion to the complexed semiquinone and accompanying equilibrium shift. This study provides a mechanistic interpretation of the interactions that lead to the formation of quinone-CO2 complexes required for the potential development of an energy efficient electrochemical separation process and discusses important considerations for practical implementation of CO2 capture in the presence of oxygen with lower vapor pressure solvents.

Developing a viable metallic lithium anode is a prerequisite for next-generation batteries. However, the low redox potential of lithium metal renders it prone to corrosion, which must be thoroughly understood for it to be used in practical energy-storage devices. Here we report a previously overlooked mechanism by which lithium deposits can corrode on a copper surface. Voids are observed in the corroded deposits and a Kirkendall-type mechanism is validated through electrochemical analysis. Although it is a long-held view that lithium corrosion in electrolytes involves direct charge-transfer through the lithium-electrolyte interphase, the corrosion observed here is found to be governed by a galvanic process between lithium and the copper substrate-a pathway largely neglected by previous battery corrosion studies. The observations are further rationalized by detailed analyses of the solid-electrolyte interphase formed on copper and lithium, where the disparities in electrolyte reduction kinetics on the two surfaces can account for the fast galvanic process.

Pancreatic ductal adenocarcinoma (PDAC) is a type of malignant tumor with high lethality. Its high tumor cell-density and large variety of extracellular matrix (ECM) components present major barriers for drug delivery. Methods: Paclitaxel-loaded PEGylated liposomes (PTX-Lip) were used as a tumor-priming agent to induce tumor cell apoptosis and decrease the abundance of ECM to promote cellular uptake and tumor delivery of nanodrugs. Paclitaxel exerts anti-cancer effects but, paradoxically, exacerbates cancer metastasis and drug resistance by increasing the expression of apoptotic B-cell lymphoma-2 protein (BCL-2). Thus, low-molecular-weight heparin-coated lipid-siRNA complex (LH-Lip/siBCL-2) was constructed to inhibit cancer metastasis and silence BCL-2 by BCL-2 siRNA (siBCL-2). Results: Significant tumor growth inhibition efficacy was observed, accompanied by obvious inhibition of cancer metastasis in vivo. Conclusion: These results suggested our sequential delivery of PTX-Lip and LH-Lip/siBCL-2 might provide a practical approach for PDAC or other ECM-rich tumors.

The development of high-efficiency nonprecious electrocatalysts based on inexpensive and Earth abundant elements is of great significance for renewable energy technologies. Group VIII transition metal phosphides (TMPs) gradually stand out due to their intriguing properties including low resistance and superior catalytic activity and stability. Herein, we adopt a unique MOF-derived strategy to synthesize transition metal phosphide nanoboxes which can be employed as electrocatalysts for the hydrogen evolution reaction. During this process, we converted a Co-MOF to a CoNi-MOF by ion exchange and low-temperature phosphating to achieve CoNiP nanoboxes. The CoNiP nanoboxes can reach a current density of 10 mA cm-2 at a low overpotential of 138 mV with a small Tafel slope of 65 mV dec-1.

Recurrence after tumor resection is mainly caused by post-operative inflammation and residual cancer cells, which is a serious obstacle to breast cancer treatment. Traditional nanoparticles rely primarily on the enhanced permeability and retention (EPR) effect in well-vascularized tumors. In this study, a macrophage-based carrier is designed to enhance the efficiency of targeting to recurrent tumors through a “dual-guide” strategy. After tumor resection, a burst of inflammatory factors occurs in the resection wound, which can recruit monocytes/macrophages rapidly. Combined with the tropism of monocyte chemoattractant protein, a large number of macrophage-mediated carriers will be recruited to surgical recurrence sites. Octaarginine (RRRRRRRR, R8)-modified liposomes in macrophages contain two agents with different pharmacological mechanisms, paclitaxel (PTX) and resveratrol (Res), which have enhanced therapeutic effects. In vitro study demonstrated that macrophage-mediated carriers approach 4 T1 cells through an inflammatory gradient and reach recurrence tumors through a “dual-guide” strategy. Then, membrane fusion and inflammation-triggered release deliver the drug into the recurrent tumor cells. In vivo experiments show that macrophage-based carriers exhibit effective tumor-targeting ability, especially in post-operation situations. More importantly, macrophage-mediated liposomes encapsulated with PTX and Res inhibit tumor recurrence in both ectopic and orthotopic 4 T1 post-operative recurrence models.

Carbon capture is essential for mitigating carbon dioxide emissions. Compared to conventional chemical scrubbing, electrochemically mediated carbon capture utilizing redox-active sorbents such as quinones is emerging as a more versatile and economical alternative. However, the practicality of such systems is hindered by the requirement of toxic, flammable organic electrolytes or often costly ionic liquids. Herein, we demonstrate that rationally designed aqueous electrolytes with high salt concentration can effectively resolve the incompatibility between aqueous environments and quinone electrochemistry for carbon capture, eliminating the safety, toxicity, and at least partially the cost concerns in previous studies. Salt-concentrated aqueous media also offer distinct advantages including extended electrochemical window, high carbon dioxide activity, significantly reduced evaporative loss and material dissolution, and importantly, greatly suppressed competing reactions including under simulated flue gas. Correspondingly, we achieve continuous carbon capture-release operations with outstanding capacity, stability, efficiency and electrokinetics, advancing electrochemical carbon separation further towards practical applications., Redox-active organic compounds that reversibly bind and release CO2 are promising candidates for carbon capture but are limited by the use of flammable, toxic aprotic electrolytes. Here the authors use salt-concentrated aqueous electrolytes in continuous CO2 separation with good performance metrics.

Metallic lithium (Li) anodes are crucial for the development of high specific energy batteries yet are plagued by their poor cycling efficiency. Electrode architecture engineering is vital for maintaining a stable anode volume and suppressing Li corrosion during cycling. In this paper, a reduced graphene oxide "host" framework for Li metal anodes is further optimized by embedding silicon (Si) nanoparticles between the graphene layers. They serve as Li nucleation seeds to promote Li deposition within the framework even without prestored Li. Meanwhile, the Li

The wetting behavior of molten liquid lithium is important to many fields of applications, especially to the Li-matrix composite anodes for batteries. Although changing the wettability of matrices has been previously shown through surface-coating, the selection criteria for suitable coating materials and optimal coating thickness and the mechanism of wettability improvement still remain unclear. Here, we study the effects of temperature, surface chemistry and surface topography on the wettability of substrates by molten liquid lithium. We summarize the following guiding principles: 1) Higher temperature decreases the viscosity of molten liquid lithium and produces smaller contact angle. 2) The wettability can be improved by coating the substrates with Li-reactive materials. The negative Gibbs free energy drives the wetting thermodynamically. The solid reaction product (Li2O) can cause kinetic barriers to wet. The contact angle decreases along with the increase of Li-reactive materials’ coating thickness since more materials give more negative Gibbs free energy. Among all the coating materials, gold shows the best wettability due to the large negative Gibbs free energy released by the Li-Au reaction thus providing a strong driving force, and the lack of solid product (Li2O) formation thus avoiding any spreading resistance of liquid lithium. 3) Substrate morphology also affects the wetting behavior of molten lithium, in way similar to water wetting. Surface roughness can increase drastically the lithiophobicity, resulting in super lithiophobic surface. These findings provide important insights in the design of Li-matrix composites and open up new opportunities for the practical application of lithium.

Summary Stretchable batteries are key components of stretchable/flexible electronic devices. However, they typically exhibit low energy density due to the low lithium storage capability. Lithium (Li) metal is the ideal anode material, but it is ductile and the unstable electrochemical performance further hinders its practical applications. Herein, for the first time, a stretchable Li metal anode with stable mechanical and electrochemical performance is fabricated. It consists of one-entity 3D-patterned Li metal microdomains connected by highly elastic polymer rubbers. Upon stretching, the rubber absorbs the mechanical energy while the electroactive Li domains are not mechanically strained. Moreover, the whole electrode is fabricated by simply winding one single Cu wire, which is facile and cost-effective. The stretchable Li metal anode is a key step in the development of novel stretchable "lithium batteries" rather than traditional stretchable "lithium-ion batteries" to boost the energy density of stretchable energy-storage devices.

Summary Effective stabilization of lithium metal has been hindered by the exacting requirements for the protection layer. Among all materials, the mechanical strength and electrochemical inertness of diamond is a prime candidate for lithium stabilization. Herein, we successfully rendered this desirable material compatible as lithium metal interface, which strictly satisfied the critical requirements. Our interface possessed the highest modulus among all the lithium coatings (>200 GPa), which can effectively arrest dendrite propagation. Since pinholes are the major failure mechanisms of artificial interfaces, a novel double-layer design was proposed to enhance the defect tolerance, enabling uniform ion flux and mechanical properties as confirmed by both simulation and experiments. Thanks to the multifold advantages of our interface design, high Coulombic efficiency of >99.4% was obtained at 1 mA cm−2; and more than 400 stable cycles were realized in prototypical lithium-sulfur cells with limited lithium, corresponding to an average anode Coulombic efficiency of >99%.

Pancreatic ductal adenocarcinoma (PDAC) is rich in cancer-associated fibroblasts (CAFs), which participate in the formation of tumor stroma. However, the dense tumor stroma of PDAC presents major barriers to drug delivery, resulting in an obstacle for PDAC therapy. Considering the special tumor microenvironment of PDAC, we constructed a novel nanoparticle which is responsive to the membrane biomarker FAP-α on CAFs and near-infrared (NIR) laser irradiation. Small sized albumin nanoparticle of paclitaxel (HSA-PTX) with strong tumor-penetration ability was encapsulated into the CAP-(a FAP-α responsive cleavable amphiphilic peptide) modified thermosensitive liposomes (CAP-TSL). Moreover, IR-780, a photothermal agent, was incorporated into CAP-TSL to afford CAP-ITSL. The designed HSA-PTX@CAP-ITSL increased the drug retention of HSA-PTX in solid tumor and HSA-PTX was released via FAP-α (specifically expresses on CAFs) triggered. Under sequential stimulation of NIR laser irradiation, IR-780 produced hyperthermia to kill tumor cells and expand the tumor interstitial space at the same time, which further promoted the release of small sized HSA-PTX in deep tumor regions. Consequently, the excellent antitumor efficacy of HSA-PTX@CAP-ITSL was demonstrated in Pan 02 subcutaneous and orthotopic tumor mouse models. Therefore, HSA-PTX@CAP-ITSL well combined chemotherapy with photothermal therapy, providing a promising drug delivery strategy for PDAC treatment.

Lithium-sulfur batteries have a high theoretical energy density of 2500 Wh/kg and are promising candidates for meeting future energy storage demands. However, dissolution of the intermediate polysulfide species into the electrolyte remains as a major challenge, causing fast capacity degradation in Li-S batteries. Many recent studies have reported various materials such as metal oxides and sulfides that interact strongly with polysulfide species and can alleviate the dissolution problem, though little work has focused on quantitative comparison of different materials under equivalent conditions. Here, we establish a standard procedure to quantitatively compare the polysulfide adsorption capability of candidate materials. We found that an order of magnitude of difference is evident between poor adsorption materials such as carbon black and strong adsorption materials such as V2O5 and MnO2. We elucidate different adsorption mechanisms may be present and probe possible adsorption species. We expect our work will provide a useful strategy to screen for suitable candidate materials and valuable information for rational design of long cycle life Li-S batteries.

Lithium–sulfur (Li–S) batteries are regarded as promising next-generation high energy density storage devices for both portable electronics and electric vehicles due to their high energy density, low cost, and environmental friendliness. However, there remain some issues yet to be fully addressed with the main challenges stemming from the ionically insulating nature of sulfur and the dissolution of polysulfides in electrolyte with subsequent parasitic reactions leading to low sulfur utilization and poor cycle life. The high flammability of sulfur is another serious safety concern which has hindered its further application. Herein, an aqueous inorganic polymer, ammonium polyphosphate (APP), has been developed as a novel multifunctional binder to address the above issues. The strong binding affinity of the main chain of APP with lithium polysulfides blocks diffusion of polysulfide anions and inhibits their shuttling effect. The coupling of APP with Li ion facilitates ion transfer and promotes the kinetics of the cathode reaction. Moreover, APP can serve as a flame retardant, thus significantly reducing the flammability of the sulfur cathode. In addition, the aqueous characteristic of the binder avoids the use of toxic organic solvents, thus significantly improving safety. As a result, a high rate capacity of 520 mAh g–1 at 4 C and excellent cycling stability of ∼0.038% capacity decay per cycle at 0.5 C for 400 cycles are achieved based on this binder. This work offers a feasible and effective strategy for employing APP as an efficient multifunctional binder toward building next-generation high energy density Li–S batteries., An aqueous inorganic polymer with strong polysulfide-trapping, favorable ion transfer, and flame-retardant property has been developed as a novel binder for safe and high energy density Li−S battery.

Hydrogen peroxide (H2O2) is a valuable chemical with a wide range of applications, but the current industrial synthesis of H2O2 involves an energy-intensive anthraquinone process. The electrochemical synthesis of H2O2 from oxygen reduction offers an alternative route for on-site applications; the efficiency of this process depends greatly on identifying cost-effective catalysts with high activity and selectivity. Here, we demonstrate a facile and general approach to catalyst development via the surface oxidation of abundant carbon materials to significantly enhance both the activity and selectivity (~90%) for H2O2 production by electrochemical oxygen reduction. We find that both the activity and selectivity are positively correlated with the oxygen content of the catalysts. The density functional theory calculations demonstrate that the carbon atoms adjacent to several oxygen functional groups (–COOH and C–O–C) are the active sites for oxygen reduction reaction via the two-electron pathway, which are further supported by a series of control experiments. The direct synthesis of hydrogen peroxide via oxygen reduction is an attractive alternative to the anthraquinone process. Here, a general trend linking oxygenation of carbon surfaces with electrocatalytic performance in peroxide synthesis is demonstrated, and computational studies provide further insight into the nature of the active sites.

Prelithiation of anode materials is an important strategy to compensate for lithium loss as a result of the formation of a solid electrolyte interphase (SEI) at the surface of anodes in lithium-ion batteries. Conventional prelithiation reagents often present serious safety concerns due to the high flammability and unstable chemical nature. Here, we successfully developed a general one-pot metallurgical process to prelithiate group IV elements and their corresponding oxides, yielding prelithiation capacity approaching the theoretical specific capacity. As-synthesized Li22Z5 alloys and Li22Z5-Li2O composites (Z = Si, Ge, Sn etc) can serve as prelithiation reagents to increase the first cycle Coulombic efficiency of both graphite and alloy-type anode materials. Among all lithiated group IV alloys, LixGe exhibits the best stability under ambient-air conditions, consistent with the simulation results showing the large binding energy between Li and Ge atoms in Li22Ge5 crystal. Metallurgical lithiation of ZO2 results in composites with homogeneously dispersed reactive LixZ nanodomains embedded in a robust Li2O matrix which effectively suppresses the oxidation process. Li22Z5-Li2O composites further improve the ambient-air stability because the strong binding between O atoms in Li2O and Li atoms in Li22Z5 stabilizes the reactive Li22Z5 nanodomains. These results allow us to identify the prelithiation reagents with the optimal stability in air, thereby simplifying the requirement on the industrial electrode fabrication environment.

Lithium polysulfide batteries possess several favorable attributes including low cost and high energy density for grid energy storage. However, the precipitation of insoluble and irreversible sulfide species on the surface of carbon and lithium (called “dead” sulfide species) leads to continuous capacity degradation in high mass loading cells, which represents a great challenge. To address this problem, herein we propose a strategy to reactivate dead sulfide species by reacting them with sulfur powder with stirring and heating (70 °C) to recover the cell capacity, and further demonstrate a flow battery system based on the reactivation approach. As a result, ultrahigh mass loading (0.125 g cm–3, 2 g sulfur in a single cell), high volumetric energy density (135 Wh L–1), good cycle life, and high single-cell capacity are achieved. The high volumetric energy density indicates its promising application for future grid energy storage., Lithium polysulfide batteries suffer from the precipitation of insoluble and irreversible sulfide species on the surface of carbon and lithium. Here the authors show a reactivation strategy by a reaction with cheap sulfur powder under stirring and heating to recover the cell capacity.

Identification of active sites for catalytic processes has both fundamental and technological implications for rational design of future catalysts. Herein, we study the active surfaces of layered lithium cobalt oxide (LCO) for the oxygen evolution reaction (OER) using the enhancement effect of electrochemical delithiation (De-LCO). Our theoretical results indicate that the most stable (0001) surface has a very large overpotential for OER independent of lithium content. In contrast, edge sites such as the nonpolar (1120) and polar (0112) surfaces are predicted to be highly active and dependent on (de)lithiation. The effect of lithium extraction from LCO on the surfaces and their OER activities can be understood by the increase of Co4+ sites relative to Co3+ and by the shift of active oxygen 2p states. Experimentally, it is demonstrated that LCO nanosheets, which dominantly expose the (0001) surface show negligible OER enhancement upon delithiation. However, a noticeable increase in OER activity (∼0.1 V i...

An all solid-state lithium-ion battery with high energy density and high safety is a promising solution for a next-generation energy storage system. High interface resistance of the electrodes and poor ion conductivity of solid-state electrolytes are two main challenges for solid-state batteries, which require operation at elevated temperatures of 60–90 °C. Herein, we report the facile synthesis of Al3+/Nb5+ codoped cubic Li7La3Zr2O12 (LLZO) nanoparticles and LLZO nanoparticle-decorated porous carbon foam (LLZO@C) by the one-step Pechini sol–gel method. The LLZO nanoparticle-filled poly(ethylene oxide) electrolyte shows improved conductivity compared with filler-free samples. The sulfur composite cathode based on LLZO@C can deliver an attractive specific capacity of >900 mAh g–1 at the human body temperature 37 °C and a high capacity of 1210 and 1556 mAh g–1 at 50 and 70 °C, respectively. In addition, the solid-state Li–S batteries exhibit high Coulombic efficiency and show remarkably stable cycling perfo...

Lithium metal is an attractive anode for the next generation of high energy density lithium-ion batteries due to its high specific capacity (3,860 mAh g–1) and lowest overall anode potential. However, the key issue is that the static solid electrolyte interphase cannot match the dynamic volume changes of the Li anode, resulting in side reactions, dendrite growth, and poor electrodeposition behavior, which prevent its practical applications. Here, we show that the “solid-liquid” hybrid behavior of a dynamically cross-linked polymer enables its use as an excellent adaptive interfacial layer for Li metal anodes. The dynamic polymer can reversibly switch between its “liquid” and “solid” properties in response to the rate of lithium growth to provide uniform surface coverage and dendrite suppression, respectively, thereby enabling the stable operation of lithium metal electrodes. We believe that this example of engineering an adaptive Li/electrolyte interface brings about a new and promising way to address the...

The nonselectivity of cell penetrating peptides had greatly limited the application in systemic administration. By conjugating a dGR motif to the C-terminal of octa-arginine, the formed tandem peptide R8-dGR had been proved to specifically recognize both integrin αvβ3 and neuropilin-1 receptors. However, the positive charge of poly-arginine would still inevitably lead to rapid clearance in the circulation system. Therefore, in this study, we tried to reduce the positive charge of poly-arginine by decreasing the number of arginine, to thus achieve improved tumor targeting efficiency. We had designed several different Rx-dGR peptides (x = 4, 6, and 8) modified liposomes and investigated their tumor targeting and penetrating properties both in vitro and in vivo. Among all the liposomes, R6-dGR modified liposomes exhibited a long circulation time similar to that of PEGylated liposomes while they retained strong penetrating ability into both tumor cells and tumor tissues, and thus had displayed the most superi...

Here, a biocompatible amphiphilic copolymer of low molecular weight heparin (LMWH) and doxorubicin (DOX) connected by an acid-sensitive hydrazone bond for enhanced tumor treatment efficacy and safety has been designed and tested. The conjugate combines DOX delivery with LMWH antimetastatic capabilities. After the nanoparticles reach the tumor site, the acidic tumor microenvironment triggers the breakage of the hydrazone bond releasing DOX from the nanoparticles, which results in an increase in the cellular uptake and enhanced in vivo antitumor efficacy. A 3.4-fold and 1.5-fold increase in tumor growth inhibition were observed compared to the saline-treated control group and free DOX treated group, respectively. The LMWH-based nanoparticles effectively inhibited interactions between tumor cells and platelets mediated by P-selectin reducing metastasis of cells in both in vitro and in vivo models. The improved safety and therapeutic effect of LMWW-DOX nanoparticles offers new potential for tumor therapy.

Herein, we demonstrate a facile method to prepare hollow-structured oxygen-vacancy-rich Fe2O3/MnO2 nanorods. Our results show that oxygen vacancies are induced by nanoscale ion intermixing between Fe and Mn ions during the annealing process. Owing to their unique core–shell hollow nanostructure and the presence of oxygen vacancies, the Fe2O3/MnO2 nanorods show excellent electrochemical performances as an anode material for lithium ion batteries and a reversible capacity higher than 700 mA h g−1 after 2000 cycles.

Tuning nanoparticle strain The catalytic activity of metals in heterogeneous catalysts can be altered by applying strain, which changes the crystalline lattice spacing and modifies the metal's electronic properties. Wang et al. show how particles of cobalt oxide, a positive electrode for lithium batteries, can expand or contract with charging and transfer strain to adsorbed platinum nanoparticles. For the oxygen reduction reaction used in fuel cells, compressive strain boosted activity by 90%, and tensile strain decreased it by 40%. Science , this issue p. 1031

Highlights Bimetallic oxides nanoparticles derived from metal–oleate complexes embedded in 3D graphene networks were fabricated by a facile and rational design approach. The unique porous architecture promotes charge transfer so as to enhance the reversible capacity. The synergetic effect between the 0D nanoparticles and 3D graphene networks plays an essential role in the superb electrochemical performance. Electronic supplementary material The online version of this article (10.1007/s40820-019-0247-3) contains supplementary material, which is available to authorized users., In this manuscript, we have demonstrated the delicate design and synthesis of bimetallic oxides nanoparticles derived from metal–oleate complex embedded in 3D graphene networks (MnO/CoMn2O4 ⊂ GN), as an anode material for lithium ion batteries. The novel synthesis of the MnO/CoMn2O4 ⊂ GN consists of thermal decomposition of metal–oleate complex containing cobalt and manganese metals and oleate ligand, forming bimetallic oxides nanoparticles, followed by a self-assembly route with reduced graphene oxides. The MnO/CoMn2O4 ⊂ GN composite, with a unique architecture of bimetallic oxides nanoparticles encapsulated in 3D graphene networks, rationally integrates several benefits including shortening the diffusion path of Li+ ions, improving electrical conductivity and mitigating volume variation during cycling. Studies show that the electrochemical reaction processes of MnO/CoMn2O4 ⊂ GN electrodes are dominated by the pseudocapacitive behavior, leading to fast Li+ charge/discharge reactions. As a result, the MnO/CoMn2O4 ⊂ GN manifests high initial specific capacity, stable cycling performance, and excellent rate capability. Electronic supplementary material The online version of this article (10.1007/s40820-019-0247-3) contains supplementary material, which is available to authorized users.

Lithium (Li) metal has long been considered the "holy grail" of battery anode chemistry but is plagued by low efficiency and poor safety due to its high chemical reactivity and large volume fluctuation, respectively. Here we introduce a new host of wrinkled graphene cage (WGC) for Li metal. Different from recently reported amorphous carbon spheres, WGC show highly improved mechanical stability, better Li ion conductivity, and excellent solid electrolyte interphase (SEI) for continuous robust Li metal protection. At low areal capacities, Li metal is preferentially deposited inside the graphene cage. Cryogenic electron microscopy characterization shows that a uniform and stable SEI forms on the WGC surface that can shield the Li metal from direct exposure to electrolyte. With increased areal capacities, Li metal is plated densely and homogeneously into the outer pore spaces between graphene cages with no dendrite growth or volume change. As a result, a high Coulombic efficiency (CE) of ∼98.0% was achieved under 0.5 mA/cm

Nanostructured hybrid metal sulfides have attracted intensive attention due to their fascinating properties that are unattainable by the single-phased counterpart. Herein, we report an efficient approach to construct cobalt sulfide/molybdenum disulfide (Co9 S8 /MoS2 ) wrapped with reduced graphene oxide (rGO). The unique structures constructed by ultrathin nanosheets and synergetic effects benefitting from bimetallic sulfides provide improved lithium ions reaction kinetics, and they retain good structural integrity. Interestingly, the conductive rGO can facilitate electron transfer, increase the electronic conductivity and accommodate the strain during cycling. When evaluated as anode materials for lithium-ion batteries (LIBs), the resultant reduced graphene oxide-coated cobalt sulfide/molybdenum disulfide (Co9 S8 /MoS2 @rGO) nanotubes deliver high specific capacities of 1140, 948, 897, 852, 820, 798 and 784 mAh g-1 at the various discharging current densities of 0.2, 0.5, 1, 2, 3, 4 and 5 A g-1 , respectively. In addition, they can maintain an excellent cycle stability with a discharge capacity of 807 mAh g-1 at 0.2 A g-1 after 70 cycles, 787 mAh g-1 at 1 A g-1 after 180 cycles and 541 mAh g-1 at 2 A g-1 after 200 cycles. The proposed method may offer fundamental understanding for the rational design of other hybrid functional composites with high Li-storage properties.

Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many kinds of cancers. However, the poor water solubility remains a serious deterrent to the utilization of CBX as a commercial drug. In this study, we designed a strategy that integrated CBX into albumin nanoparticles (ANs) formed with human serum albumin (HSA) to improve the water solubility and targeting ability. Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could cooperate with CBX to enhance the antitumor effect. The obtained ANs containing ICG and CBX (AN-ICG-CBX) exhibited good mono-dispersity. In vitro cytotoxicity study showed the effectiveness of CBX and ICG, respectively, whereas AN-ICG-CBX with irradiation exhibited the most efficient antiproliferative ability (83.7%). In vivo safety evaluation studies demonstrated the safety of AN-ICG-CBX. Furthermore, the in vivo antitumor study indicated that the AN-ICG-CBX with irradiation achieved higher tumor inhibition rate (91.3%) compared with CBX-encapsulated AN (AN-CBX) (83.3%) or ICG-encapsulated AN (AN-ICG) plus irradiation (60.1%) in 4T1 tumor-bearing mice. To sum up, a safety and effective formulation AN-ICG-CBX was developed in this study and successfully reduced the drug toxicity, improved the targeting efficiency and enhanced the therapeutic effects, becoming a promising candidate for clinical application.

Safe operation is crucial for lithium (Li) batteries, and therefore, developing separators with dendrite-detection function is of great scientific and technological interest. However, challenges have been encountered when integrating the function into commercial polyolefin separators. Among all polymer candidates, polyimides (PIs) are prominent due to their good thermal/mechanical stability and electrolyte wettability. Nevertheless, it is still a challenge to efficiently synthesize PI separators, let alone integrate additional functions. In this work, a novel yet facile solution synthesis was developed to fabricate a nanoporous PI separator. Specifically, recyclable LiBr was utilized as the template for nanopores creation while the polymer was processed at the intermediate stage. This method proves not only to be a facile synthesis with basic lab facility but also to have promising potential for low-cost industrial production. The as-synthesized PI separator exhibited excellent thermal/mechanical stability and electrolyte wettability, the latter of which further improves the ionic conductivity and thus battery rate capability. Notably, stable full-cell cycling for over 200 cycles with a PI separator was further achieved. Based on this method, the fabrication of an all-integrated PI/Cu/PI bifunctional separator for dendrite detection can be fulfilled. The as-fabricated all-integrated separators prove efficient as early alarms of Li penetration, opening up the opportunity for safer battery design by separator engineering.

Metallic lithium is a promising anode candidate for future high-energy-density lithium batteries. It is a light-weight material, and has the highest theoretical capacity (3,860 mAh g–1) and the lowest electrochemical potential of all candidates. There are, however, at least three major hurdles before lithium metal anodes can become a viable technology: uneven and dendritic lithium deposition, unstable solid electrolyte interphase and almost infinite relative dimension change during cycling. Previous research has tackled the first two issues, but the last is still mostly unsolved. Here we report a composite lithium metal anode that exhibits low dimension variation (∼20%) during cycling and good mechanical flexibility. The anode is composed of 7 wt% ‘lithiophilic’ layered reduced graphene oxide with nanoscale gaps that can host metallic lithium. The anode retains up to ∼3,390 mAh g–1 of capacity, exhibits low overpotential (∼80 mV at 3 mA cm–2) and a flat voltage profile in a carbonate electrolyte. A full-cell battery with a LiCoO2 cathode shows good rate capability and flat voltage profiles. Volumetric changes during cycling in lithium metal anodes can be largely suppressed by using a lithophilic carbonaceous host.

High ionic conductivity solid polymer electrolyte (SPE) has long been desired for the next generation high energy and safe rechargeable lithium batteries. Among all of the SPEs, composite polymer electrolyte (CPE) with ceramic fillers has garnered great interest due to the enhancement of ionic conductivity. However, the high degree of polymer crystallinity, agglomeration of ceramic fillers, and weak polymer-ceramic interaction limit the further improvement of ionic conductivity. Different from the existing methods of blending preformed ceramic particles with polymers, here we introduce an in situ synthesis of ceramic filler particles in polymer electrolyte. Much stronger chemical/mechanical interactions between monodispersed 12 nm diameter SiO2 nanospheres and poly(ethylene oxide) (PEO) chains were produced by in situ hydrolysis, which significantly suppresses the crystallization of PEO and thus facilitates polymer segmental motion for ionic conduction. In addition, an improved degree of LiClO4 dissociation can also be achieved. All of these lead to good ionic conductivity (1.2 × 10(-3) S cm(-1) at 60 °C, 4.4 × 10(-5) S cm(-1) at 30 °C). At the same time, largely extended electrochemical stability window up to 5.5 V can be observed. We further demonstrated all-solid-state lithium batteries showing excellent rate capability as well as good cycling performance.

The use of pH-responsive cell-penetrating peptides (CPPs) is an attractive strategy for drug delivery in vivo, however, they still could not actively target to the desired sites. Here, we designed a pH-responsive CPP (TR) with the ability of active targeting to integrin αvβ3, which was a tandem peptide consisted of active targeting ligand peptide (c(RGDfK)) and pH-responsive CPP (TH). The targeting efficiency of TR with integrin was evaluated by molecular simulation and docking studies. The affinity assays of TR peptide modified liposomes (TR-Lip) at pH7.4 and pH6.5 demonstrated adequately the pH-responsive binding efficacy of TR-Lip with integrin αvβ3. The cellular uptake of CFPE-labeled TR-Lip on integrin αvβ3-overexpressing B16F10 cells was 41.67-, 30.67-, and 11.90-fold higher than that of CFPE-labeled PEG-, RGD-, and TH-modified liposomes at pH6.5, respectively, suggesting that TR-Lip could not only actively target to αvβ3-overexpressing cells compared to TH-Lip, but also significantly increased cellular uptake compared to RGD-Lip. At the concentration of 20μg/mL paclitaxel (PTX), the killing activity of PTX-loaded TR-Lip (PTX-TR-Lip) against B16F10 cells was 1.80-, 1.45-, 1.30-, 1.15-time higher than that of PTX-loaded PEG-, RGD-, TH-modified liposomes and free PTX at pH6.5, respectively. In vivo imaging displayed the maximum accumulation of DiD-labeled TR-Lip at tumor sites compared to the other groups. Tumor inhibition rate of B16F10 tumor-bearing mice treated with PTX-TR-Lip was 85.04%, relative to that of PBS. In B16F10 tumor-bearing mice, PTX-TR-Lip showed significantly higher survival rate compared with the other groups. Collectively, all the results in vitro and in vivo suggested that TR-Lip would be a potential delivery system for PTX to treat integrin αvβ3-overexpressing tumor-bearing mice.

Herein, we developed a hierarchical bio-composite sensing film by facile one-step electro-deposition of 0D enzyme-polymer nanoparticles (NPs) with 2D graphene oxide nanosheets as conductive supports and nanofillers, based on which an effective and robust enzymatic biosensor platform was constructed. Horseradish peroxidase (HRP) as a model enzyme was co-assembled with a photo-cross-linkable polypeptide of 2-hydroxyethyl methacrylate modified poly(γ-glutamic acid) (γ-PGA-HEMA), generating hybrid HRP@γ-PGA-HEMA nanoparticles (HRP@PGH NPs). Then HRP@PGH NPs and graphene oxide nanosheets (GO NSs) were simultaneously electrodeposited onto the electrode surface, obtaining a hierarchical 0D-2D bio-composite film. After subsequent electrochemical reduction of GO NSs into graphene nanosheets (GNSs) and following photo-cross-linking, the resultant nanostructured HRP@PGH/GNSs sensing film was successfully applied to construct an enzymatic biosensor for hydrogen peroxide (H2O2). The biosensor exerted high sensitivity, fast response, and good stability for H2O2 sensing. Satisfactory results were also demonstrated for its practical application in human serum samples, suggesting a promising application potential in biomedical diagnostics. The one-step generated 0D-2D bio-composite sensing film demonstrates synergetic effects from both the soft nanoparticles and hard conductive nanosheets, which would enlighten the innovative construction of composite nanomaterials and nanoarchitectonics for bio-sensing systems.

AmBisome® is a liposomal formulation of amphotericin B (Amp B), a complex parenteral antifungal product with no US FDA approved generic version available to date. For generic Amp B liposomal product development, examination of the drug release profile is important for product quality control and analytical comparability evaluation with the reference listed drug. Yet, there is no standardized in vitro drug release (IVR) assay currently available for Amp B liposomes. In this study, we describe the development of a USP-4 apparatus-based IVR assay capable of discriminating liposomal Amp B formulations based on the drug release profile. The goal of the IVR assay development was to identify release media compositions and assay temperatures capable of facilitating 70–100% of drug release from AmBisome® in 24 h without Amp B precipitation or disruption of liposome structure. We found that an addition of 5% w/v of γ-cyclodextrin to the release media of 5% sucrose, 10 mM HEPES, and 0.01% NaN3 (pH = 7.4) prevented Amp B precipitation and facilitated drug release. Increased IVR assay temperature led to increased drug release rate, and 55 °C was selected as the highest temperature that induced drug release close to our target without causing product precipitation. The developed IVR assay was used to discriminate between drug release rates from AmBisome® and micellar Amp B products like Fungizone® and Fungcosome. The IVR assay was also capable of discriminating between Amp B liposomes with the same composition as AmBisome® but prepared by either extrusion or homogenization processes, both of which resulted in measurable liposomal particle size heterogeneity and Amp B concentration differences. Finally, the USP-4 IVR assay was used to compare Amp B release profiles between AmBisome® and two generic products approved in India, Amphonex® (Bharat Serums and Vaccines Ltd.) (f2 = 66.3) and Phosome® (Cipla Ltd.) (f2 = 55.4). Taken together, the developed USP-4 IVR assay can be a useful tool for drug release profile characterization in generic liposomal Amp B formulation development.

We summarize the origins of lithium-ion battery safety issues and discuss recent progress in materials design to improve safety., Lithium-ion batteries (LIBs) are considered to be one of the most important energy storage technologies. As the energy density of batteries increases, battery safety becomes even more critical if the energy is released unintentionally. Accidents related to fires and explosions of LIBs occur frequently worldwide. Some have caused serious threats to human life and health and have led to numerous product recalls by manufacturers. These incidents are reminders that safety is a prerequisite for batteries, and serious issues need to be resolved before the future application of high-energy battery systems. This Review aims to summarize the fundamentals of the origins of LIB safety issues and highlight recent key progress in materials design to improve LIB safety. We anticipate that this Review will inspire further improvement in battery safety, especially for emerging LIBs with high-energy density.

Among all solid electrolytes, composite solid polymer electrolytes, comprised of polymer matrix and ceramic fillers, garner great interest due to the enhancement of ionic conductivity and mechanical properties derived from ceramic–polymer interactions. Here, we report a composite electrolyte with densely packed, vertically aligned, and continuous nanoscale ceramic–polymer interfaces, using surface-modified anodized aluminum oxide as the ceramic scaffold and poly(ethylene oxide) as the polymer matrix. The fast Li+ transport along the ceramic–polymer interfaces was proven experimentally for the first time, and an interfacial ionic conductivity higher than 10–3 S/cm at 0 °C was predicted. The presented composite solid electrolyte achieved an ionic conductivity as high as 5.82 × 10–4 S/cm at the electrode level. The vertically aligned interfacial structure in the composite electrolytes enables the viable application of the composite solid electrolyte with superior ionic conductivity and high hardness, allowin...

High-energy all-solid-state lithium (Li) batteries have great potential as next-generation energy-storage devices. Among all choices of electrolytes, polymer-based systems have attracted widespread attention due to their low density, low cost, and excellent processability. However, they are generally mechanically too weak to effectively suppress Li dendrites and have lower ionic conductivity for reasonable kinetics at ambient temperature. Herein, an ultrastrong reinforced composite polymer electrolyte (CPE) is successfully designed and fabricated by introducing a stiff mesoporous SiO2 aerogel as the backbone for a polymer-based electrolyte. The interconnected SiO2 aerogel not only performs as a strong backbone strengthening the whole composite, but also offers large and continuous surfaces for strong anion adsorption, which produces a highly conductive pathway across the composite. As a consequence, a high modulus of ≈0.43 GPa and high ionic conductivity of ≈0.6 mS cm-1 at 30 °C are simultaneously achieved. Furthermore, LiFePO4 -Li full cells with good cyclability and rate capability at ambient temperature are obtained. Full cells with cathode capacity up to 2.1 mAh cm-2 are also demonstrated. The aerogel-reinforced CPE represents a new design principle for solid-state electrolytes and offers opportunities for future all-solid-state Li batteries.

Nanoparticles (NPs) offer new solutions for the diagnosis and treatment of tumors. However, the anti-tumor effect has not been greatly improved. Tumors are easily spread through the lymphatic system while the traditional NPs (~100 nm) can hardly reach lymph nodes for the treatment of metastasis. In addition, the NPs with fixed particle size cannot achieve efficient “penetration” and long-term “retention” simultaneously. Herein, we established “transformable” micelles modified with azide/alkyne groups for click chemical reaction. Not surprisingly, the small micelles (~25 nm) could effectively target lymph nodes, limiting the growth of the metastases associated with their size-regulated abilities to extravasate from the vasculature. Tumor lymph node metastasis dropped by 66.7%. After reaching primary tumors, cycloaddition reaction occurred between groups on micelles, resulting in the formation of aggregates. The strategy resulted in improved retention of the micelles in 4 T1 cells both in vitro and in vivo owing to the decreasing of nanoparticle exocytosis and minimizing the backflow to the bloodstream. Enhanced cytotoxicity on 4 T1 cells and improved antitumor efficacy were also observed. S-PTX (+) exhibited 76.23% tumor suppression, and tumor mass at the end of the treatment also showed the best tumor inhibitory effect. In conclusion, this drug delivery system provides a strategy for effective treatment of the primary tumor and lymphatic metastasis.

The development of next-generation lithium-based rechargeable batteries with high energy density, low cost, and improved safety is a great challenge with profound technological significance for portable electronics, electric vehicles, and grid-scale energy storage. Specifically, advanced lithium battery chemistries call for a paradigm shift to electrodes with high Li to host ratio based on a conversion or alloying mechanism, where the increased capacity is often accompanied by drastic volumetric changes, significant bond breaking, limited electronic/ionic conductivity, and unstable electrode/electrolyte interphase. Fortunately, the rapid progress of nanotechnology over the past decade has been offering battery researchers effective means to tackle some of the most pressing issues for next-generation battery chemistries. The major applications of nanotechnology in batteries can be summarized as follows: First, by reduction of the dimensions of the electrode materials, the cracking threshold of the material upon lithiation can be overcome, at the same time facilitating electron/ion transport within the electrode. Second, nanotechnology also provides powerful methods to generate various surface-coating and functionalization layers on electrode materials, protecting them from side reactions in the battery environment. Finally, nanotechnology gives people the flexibility to engineer each and every single component within a battery (separator, current collector, etc.), bringing novel functions to batteries that are unachievable by conventional methods. Thus, this Account aims to highlight the crucial role of nanotechnology in advanced battery systems. Because of the limited space, we will mainly assess representative examples of rational nanomaterials design with complexity for silicon and lithium metal anodes, which have shown great promise in constraining their large volume changes and the repeated solid-electrolyte interphase formation during cycling. Noticeably, the roadmap delineating the gradual improvement of silicon anodes with a span of 11 generations of materials designs developed in our group is discussed in order to reflect how nanotechnology could guide battery research step by step toward practical applications. Subsequently, we summarize efforts to construct nanostructured composite sulfur cathodes with improved electronic conductivity and effective soluble species encapsulation for maximizing the utilization of active material, cycle life, and system efficiency. We emphasize carbon-based materials and, importantly, materials with polar surfaces for sulfur entrapment. We then briefly discuss nanomaterials strategies to improve the ionic conductivity of solid polymer electrolytes by means of incorporating high-surface-area and, importantly, high-aspect-ratio secondary-phase fillers for continuous, low-tortuosity ionic transport pathways. Finally, critical innovations that have been brought to the area of grid-scale energy storage and battery safety by nanotechnology are also succinctly reviewed.

Preeclampsia is one of the most serious pregnancy complications. Many animal models have already been developed by researchers to study the pathogenesis and treatment of preeclampsia. However, most of these animal models were established by systemic administration or by surgery in the uterine cavity, which could lead to unwanted systemic toxicity or operative wounds and affect the accuracy of the results. Because of the high expression level of integrin αvβ3 on the placenta, arginine-glycine-aspartic acid peptide (RGD) modified PEGylated cationic liposome (RGD-Lip) was designed as a novel gene delivery system to target the placenta safely and efficiently, and a new animal model of preeclampsia was established through targeting of long noncoding RNA (lncRNA). The results of cellular uptake and endosomal localization showed that RGD-Lip enhanced cellular uptake and endosomal escape of small interfering RNA (siRNA) on HTR-8/SVneo. In vivo imaging revealed that RGD-Lip was selectively delivered to the placenta. Additionally, H19x siRNA was efficiently transferred into the placenta of C57BL/6 mice via the injection of H19x siRNA-loaded RGD-Lip, which could result in the occurrence of preeclampsia-like symptoms. In summary, RGD-Lip provided a platform to efficiently deliver siRNA to the placenta, and a new preeclampsia-like mouse model was developed targeting placenta enriched/specific genes, including noncoding RNAs.

Retro-inverso peptide represented the isomer of a parent peptide in which the direction of the sequence was reversed and the chirality of each amino acid residue was inverted. Generally, retro-inverso peptides possessed equal or even higher activities compared to the original peptide. RGD was a commonly used ligand for tumor and vascular targeting due to its affinity to integrin αvβ3 receptors. The biological activity study of the isomers of RGD would indeed provide useful suggestions for the design of tumor targeting peptides. Therefore, the tumor targeting activities of octa-arginine which was modified with different retro-inverso sequences of RGD peptide were investigated in this study. Three different tandem peptides (R8-GDGR, R8-GdGr and R8-GdGR) were designed on the basis of R8-GRGD. The tumor targeting activities of these tandem peptides were evaluated both in vitro and in vivo. Finally, R8-GdGR displayed selective binding affinity to integrin αvβ3 at the cellular level, and exhibited efficient tumor homing and penetrating capabilities in vivo. Meanwhile, R8-GdGR also showed stronger neovessel targeting ability compared to the others. In conclusion, all the results demonstrated that dGR possessed similar biological activity to RGD and was a potential ligand for further designing of tumor targeting peptides.

Hybrid nanoparticles consisting of lipids and the biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), were developed for the targeted delivery of the anticancer drug, docetaxel. Transmission electron microscopic observations confirmed the presence of a lipid coating over the polymeric core. Using coumarin-6 as a fluorescent probe, the uptake efficacy of RGD conjugated lipid coated nanoparticles (RGD-L-P) by C6 cells was increased significantly, compared with that of lipid-polymer hybrid nanoparticles (L-P; 2.5-fold higher) or PLGA-nanoparticles (PLGA-P; 1.76-fold higher). The superior tumor spheroid penetration of RGD-L-P indicated that RGD-L-P could target effectively and specifically to C6 cells overexpressing integrin α(v)β3. The anti-proliferative activity of docetaxel-loaded RGD-L-P against C6 cells was increased 2.69- and 4.13-fold compared with L-P and PLGA-P, respectively. Regarding biodistribution, the strongest brain-localized fluorescence signals were detected in glioblastoma multiforme (GBM)-bearing rats treated with 1,10-Dioctadecyl-3,3,30,30-tetramethylindotricarb-ocyanine iodide (DiR)-loaded RGD-L-P, compared to rats treated with DiR-loaded L-P or PLGA-P. The median survival time of GBM-bearing rats treated with docetaxel-loaded RGD-L-P was 57 days, a fold increase of 1.43, 1.78, 3.35, and 3.56 compared with animals given L-P (P < 0.05), PLGA-P (P < 0.05), Taxotere (P < 0.01) and saline (P < 0.01), respectively. Collectively, these results support RGD-L-P as a promising drug delivery system for the specific targeting and the treatment of GBM.

The oxygen evolution reaction is of paramount importance in clean energy generation and storage. While the common approach in search of active, durable and cost-effective oxygen evolution catalysts involves the development of novel materials, it is equally important to tune the properties of existing materials so as to improve their catalytic performance. Here, we demonstrate the general efficacy of electrochemical lithium tuning in organic electrolyte on enhancing the oxygen evolution catalytic activity of olivine-type lithium transition metal phosphates, a widely-researched family of cathode materials in lithium ion batteries. By continuously extracting lithium ions out of lithium transition metal phosphates, the materials exhibited significantly enhanced water oxidation catalytic activity. Particularly, the electrochemically delithiated Li(Ni,Fe)PO4 nanoparticles anchored on reduced graphene oxide sheets afforded outstanding performance, generating a current density of 10 mA cm−2 at an overpotential of only 0.27 V for over 24 h without degradation in 0.1 M KOH, outperforming the commercial precious metal Ir catalysts.