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To boost the use of electronic devices and driving mileage of electric vehicles, it is urgent to develop lithium-ion batteries (LIBs) with higher energy density and longer life. High-voltage and hi...

The Li-O2 battery based on the polymer electrolyte has been considered as the feasible solution to the safety issue derived from the liquid electrolyte. However, the practical application of the polymer electrolyte-based Li-O2 battery is impeded by the poor cyclability and unsatisfactory energy efficiency caused by the structure of the porous cathode. Herein, an architecture of a composite cathode with improved oxidation kinetics of discharge products was designed by an in situ method through the polymerization of the electrolyte precursor for the polymer-based Li-O2 battery. The composite cathode can provide sufficient gas diffusion channels, abundant reaction active sites, and continuous pathways for ion diffusion and electron transport. Furthermore, the oxidation kinetics of nanosized discharge products formed in the composite cathode can be improved by hexamethylphosphoramide during the recharge process. The polymer-based Li-O2 batteries with the composite cathode demonstrate highly reversible capacity when fully charged and a long cycle lifetime under a fixed capacity with low overpotentials. Moreover, the interface contact between hexamethylphosphoramide and the Li metal can be stabilized simultaneously. Therefore, the composite cathode architecture designed in this work shows a promising application in high-performance polymer-based Li-O2 batteries.

Neoantigen-based cancer vaccines are promising for boosting cytotoxic T lymphocyte (CTL) responses. However, the therapeutic effect of cancer vaccines is severely blunted by functional suppression of the dendritic cells (DCs). Herein, we demonstrated an acid-responsive polymeric nanovaccine for activating the stimulator of interferon genes (STING) pathway and improving cancer immunotherapy. The nanovaccines were fabricated by integrating an acid-activatable polymeric conjugate of the STING agonist and neoantigen into one single nanoplatform. The nanovaccines efficiently accumulated at the lymph nodes for promoting DC uptake and facilitating cytosol release of the neoantigens. Meanwhile, the STING agonist activated the STING pathway in the DCs to elicit interferon-β secretion and to boost T-cell priming with the neoantigen. The nanovaccine dramatically inhibited tumor growth and occurrence of B16-OVA melanoma and 4T1 breast tumors in immunocompetent mouse models. Combination immunotherapy with the nanovaccines and anti-PD-L1 antibody demonstrated further improved antitumor efficacy in a 4T1 breast tumor model.

Lithium-rich layered oxides (LLOs) are one of the attractive cathodes for high-energy lithium-ion batteries (LIBs). However, their rate performance and cycling stability, especially at high tempera...

Traditional technologies for the recycling of spent lithium-ion batteries (LIBs) mainly focus on reductive leaching, which often leads to total leaching rather than selective leaching of metals. As...

The importance of the immune system in cancer therapy has been reaffirmed by the success of the immune checkpoint blockade. The complex tumor microenvironment and its interaction with the immune system, however, remain mysteries. Molecular imaging may shed light on fundamental aspects of the immune response to elucidate the mechanism of cancer immunotherapy. In this review, we discuss various imaging approaches that offer in-depth insight into the tumor microenvironment, checkpoint blockade therapy, and T cell-mediated antitumor immune responses. Recent advances in the molecular imaging modalities, including magnetic resonance imaging (MRI), positron electron tomography (PET), and optical imaging (e.g., fluorescence and intravital imaging) for in situ tracking of the immune response, are discussed. It is envisaged that the integration of imaging with immunotherapy may broaden our understanding to predict a particular antitumor immune response.

The accurate detection of tumorous methylglyoxal (MGO) and its detoxifier glyoxalase 1 (GLO1) in living systems is critical for understanding their roles in tumor initiation and progression. To date, the in situ fluorescence detection of endogenous MGO and GLO1 in tumor has not been reported. Herein we developed a near-infrared (NIR) fluorescent probe MEBTD to specifically detect tumorous MGO. Compared with previously reported MGO fluorescent probes, MEBTD exhibits several distinct advantages, including NIR emission, high selectivity with an MGO detection limit of 18 nM, and a 131-fold off-on ratio. The probe could sense GLO1 activity and monitor the therapeutic effect of GLO1 inhibitors by imaging tumorous MGO in a both a real-time and in situ manner, demonstrating that the biological effect of GLO1 inhibitors is dependent on the GLO1 activity. Furthermore, MEBTD enables the visualization of tumorous MGO induced by GLO1 inhibitors in vivo. To the best of our knowledge, MEBTD is the first NIR fluorescent probe for specifically imaging tumorous MGO in living animals, indicating the promising potential for tumor diagnosis and therapeutic evaluation.

The development of silicon-based anode materials is important for improving the energy density of current lithium ion batteries. However, there are still strong demands for these materials with better cycle stability and higher reversible capacity. Here, a kind of dual bond restricted MXene-Si-CNT composite anode materials with enhanced electrochemical performance is reported. These dual bonds have been clearly revealed by an X-ray photoelectron spectroscopy technique and also proven by theoretical calculations with spontaneous reaction energy values (-0.190 and -0.429 eV/atom for Ti-Si and C-Si bonds, respectively). The cycle stability of the composites, prepared by a facile ball-milling synthetic method, can obviously be improved because of the existence of these dual bonds and the multidimensional constructed architecture. The MXene-Si-CNT composite with 60 wt % silicon possesses the best overall performance, with ∼80% capacity retention after 200 cycles, and achieves 841 mAh g-1 at 2 A g-1. This approach demonstrates a promising strategy to exploit high-performance anode materials and lessens the immanent negative effect of silicon-based materials. Furthermore, it is significant to extend this method to other anode materials with serious volumetric change problems during the cycling process.

Advanced anode materials possessing high performance, excellent stability, and low cost are quite insufficient for sodium ion batteries (NIBs), and there is a call for huge progress to meet the pre...

Lithium-rich layered oxide materials are extremely important for improving the energy density of lithium-ion batteries. However, the electrochemical kinetics and cycle stability of these materials ...

Cathodes of lithium-rich layered oxides for high-energy Li-ion batteries in electrically powered vehicles are attracting considerable attention by the research community. However, current research is insufficient to account for their complex reaction mechanism and application. Here, the structural evolution of lithium–manganese-rich layered oxides at different temperatures during electrochemical cycling has been investigated thoroughly, and their structural stability has been designed. The results indicated structure conversion from the two structures into a core–shell structure with a single distorted-monoclinic LiTMO2 structure core and disordered-spinel/rock salt structure shell, along with lattice oxygen extraction and lattice densification, transition- metal migration, and aggregation on the crystal surface. The structural conversion behavior was found to be seriously temperature sensitive, accelerated with higher temperature, and can be effectively adjusted by structural design. This study clarifies...

To accurately monitor the variations of lysosomal nitric oxide (NO) under physiological condition remains a great challenge for understanding the biological function of NO. Herein, we developed a new chemotype probe, namely, MBTD, for acid-promoted and far-red fluorescence imaging of lysosomal NO in vitro and ex vivo. MBTD was rationally designed by incorporating o-phenylenediamino (OPD) moiety into the donor-acceptor-donor (D-A-D) type fluorophore based on a dual intramolecular charge transfer (ICT) mechanism. Compared to previously reported OPD-based NO probes, MBTD displays several distinct advantages including large stroke shift, huge on-off ratio with minimal autofluorescence, and high NO specificity. Particularly, MBTD exhibits an acid-promoted response to NO with high acid tolerance, which greatly improves the spatial resolution to lysosomal NO by excluding the background noise from other nonacidic organelles. Furthermore, MBTD displayed much longer-lived and more stable fluorescence emission in comparison with the commercialized NO probe. MBTD was employed for ratiometric examination of the exogenous or endogenous NO of macrophages. More importantly, MBTD was able to detect the variation of lysosomal NO level in an acute liver injury mouse model ex vivo, implying the potential of MBTD for real-time monitoring the therapeutic efficacy of drug candidates for the treatment of acute liver injury. MBTD as a novel type of NO probe might open a new avenue for precisely sensing lysosomal NO-related pathological and therapeutic process.

Metastasis causes high mortality of breast cancer, and the inability of drug delivery to metastatic sites remains a crucial challenge for antimetastasis therapy. Herein, we report that inflammatory monocytes loading legumain-activated nanoparticles can actively target lung metastases and initiate metastasis-specific intelligent drug release for antimetastasis therapy. The cytotoxic mertansine is conjugated to poly(styrene-co-maleic anhydride) with a legumain-sensitive peptide and self-assembled into nanoparticles (SMNs), and then loaded into inflammatory monocytes to prepare the SMNs-loaded monocytes delivery system (M-SMNs). M-SMNs would be in living state in circulation to ensure their active targeting to lung metastases, and responsively damaged at the metastatic sites upon the differentiation of monocytes into macrophages. The anticancer drugs are intelligently released from M-SMNs as free drug molecules and drug-loaded microvesicles, resulting in considerable inhibition on the proliferation, migration, and invasion activities of metastatic 4T1 breast cancer cells. Moreover, M-SMNs significantly improve the delivery to lung metastases and penetrate the metastatic tumors, thus producing a 77.8% inhibition of lung metastases. Taken together, our findings provide an intelligent biomimetic drug delivery strategy via the biological properties of inflammatory monocytes for effective antimetastasis therapy.

The success of cancer chemotherapy is impeded by poor drug delivery efficiency due to the existence of a series of pathophysiological barriers in the tumor. In this study, we reported a tumor acidity-triggered ligand-presenting (ATLP) nanoparticle for cancer therapy. The ATLP nanoparticles were composed of an acid-responsive diblock copolymer as a sheddable matrix and an iRGD-modified polymeric prodrug of doxorubicin (iPDOX) as an amphiphilic core. A PEG corona of the polymer matrix protected the iRGD ligand from serum degradation and nonspecific interactions with the normal tissues while circulating in the blood. The ATLP nanoparticles specifically accumulated at the tumor site through the enhanced permeability and retention (EPR) effect, followed by acid-triggered dissociation of the polymer matrix within the tumoral acidic microenvironment (pH ∼ 6.8) and subsequently exposing the iRGD ligand for facilitating tumor penetration and cellular uptake of the PDOX prodrug. Additionally, the acid-triggered dissociation of the polymer matrix induced a 4.5-fold increase of the fluorescent signal for monitoring nanoparticle activation in vivo. Upon near-infrared (NIR) laser irradiation, activation of Ce6-induced significant reactive oxygen species (ROS) generation, promoted drug diffusion inside the tumor mass and circumvented the acquired drug resistance by altering the gene expression profile of the tumor cells. The ATLP strategy might provide a novel insight for cancer nanomedicine.

The stimuli-responsive polymeric nanocarriers have been studied extensively, and their structural changes in cells are important for the controlled intracellular drug release. The present work reported RGD-dextran/purpurin 18 conjugates with pH-responsive phenylboronate as spacer for monitoring the structural change of nanovehicles through ratiometric photoacoustic (PA) signal. Phenylboronic acid modified purpurin 18 (NPBA-P18) could attach onto the RGD-decorated dextran (RGD-Dex), and the resulting RGD-Dex/NPBA-P18 (RDNP) conjugates with different molar ratios of RGD-Dex and NPBA-P18 were prepared. When the moles of NPBA-P18 were equivalent to more than triple of RGD-Dex, the single-stranded RDNP conjugates could self-assemble into nanoparticles in aqueous solution due to the fairly strong hydrophobicity of NPBA-P18. The pH-responsive aggregations of NPBA-P18 were investigated by UV-vis, fluorescence, and circular dichroism spectra, as well as transmission electron microscope. Based on distinct PA signals between monomeric and aggregated state, ratiometric PA signal of I750/I710 could be presented to trace the structural change progress. Compared with RDNP single chains, the nanoparticles exhibited effective cellular internalization through endocytosis pathway. Furthermore, the nanoparticles could form well-ordered aggregates responding to intracellular acidic environment, and the resulting structural change was also monitored by ratiometric PA signal. Therefore, the noninvasive PA approach could provide a deep insight into monitoring the intracellular structural change process of stimuli-responsive nanocarriers.

Cancer metastasis leads to high mortality of breast cancer and is difficult to treat because of the poor delivery efficiency of drugs. Herein, we report the wrapping of a drug-carrying liposome with an isolated macrophage membrane to improve delivery to metastatic sites. The macrophage membrane decoration increased cellular uptake of the emtansine liposome in metastatic 4T1 breast cancer cells and had inhibitory effects on cell viability. In vivo, the macrophage membrane enabled the liposome to target metastatic cells and produced a notable inhibitory effect on lung metastasis of breast cancer. Our results provide a biomimetic strategy via the biological properties of macrophages to enhance the medical performance of a nanoparticle in vivo for treating cancer metastasis.

Metastasis is the primary cause resulting in the high mortality of breast cancer. The inherent antimetastasis bioactivity of Pluronic copolymers with a wide range of hydrophilic-lipophilic balance (HLB) including Pluronic L61, P85, P123, F127, F68, and F108 was first explored on metastatic 4T1 breast cancer cells. The results indicated that P85 and P123 could strongly inhibit the migration and invasion of 4T1 cells. The effects of the polymers on cell healing, migration, and invasion exhibited bell-shaped dependencies on HLB of Pluronic copolymers, and the better antimetastasis effects of Pluronic copolymers could be achieved with the HLB between 8 and 16. P85 and P123 themselves could significantly inhibit pulmonary metastasis in 4T1 mammary tumor metastasis model in situ. In addition, a synergetic antimetastasis effect could be achieved during drug combination of doxorubicin hydrochloride (DOX) and P85 or P123 intravenously. The metastasis effects of P85 and P123 both in vitro and in vivo were partially attributed to the downregulation of matrix metalloproteinase-9 (MMP-9). Therefore, Pluronic copolymers with moderate HLB 8-16 such as P85 and P123 could be promising excipients with therapeutics in drug delivery systems to inhibit breast cancer metastasis.

TiO2–Y2O3 core–shell nanoparticles for dye-sensitized solar cells (DSSCs) have been fabricated by a solvothermal technique. The heterostructure of TiO2 nanoparticles coated with porous Y2O3 is conf...

An acidic leaching method using HNO3 is widely employed to release the global fallout Pu from soil samples for further chemical separations in radioecology and toxicology studies and in many applications using Pu as a useful tracer. In the method's sample ash treatment step to decompose organic matter in soil, various ashing temperatures (400-900 °C) are used; however, the effect of ashing temperature on the accurate Pu analysis has not been well investigated. In this study, two standard reference soils (IAEA-soil-6 and IAEA-375) were used to determine the ashing temperature effect (from 375 to 600 °C) on the HNO3 leaching method. The Pu analytical results of both standard reference materials showed that lower (239+240)Pu activity was observed when the ashing temperature exceeded 450 °C, and the (239+240)Pu activity continued to decrease as the ashing temperature was raised. Approximately 40% of the Pu content could not be leached out by concentrated HNO3 after ashing for 4 h at 600 °C. The Pu loss was attributed to the formation of refractory materials, which are insoluble in HNO3 solution. This hypothesis was confirmed by the XRD analysis of soil samples, which revealed that plagioclase-like silicate materials were formed after high-temperature ashing. To ensure Pu release efficiency in HNO3 leaching, we recommend 450 °C as the ideal ashing temperature. This recommendation is also useful for analysis of other important artificial radionuclides (e.g., (137)Cs, (90)Sr, (241)Am) for which an ashing process is needed to decompose the organic content in soil samples.

The development of multidrug resistance (MDR) in human hepatocellular carcinoma (HCC) is one of the major obstacles for successful chemotherapy of HCC. Co-delivery of sorafenib (SF) and survivin shRNA (shSur) was postulated to achieve synergistic effects in reversing MDR, suppressing tumor growth and angiogenesis. For this purpose, in this work, SF and shSur co-loaded pluronic P85-polyethyleneimine/d-α-tocopheryl polyethylene glycol 1000 succinate nanocomplexes (SSNs) were first designed and developed for the treatment of drug resistant HCC. The experimental results showed that SSNs could achieve effective cellular internalization and shSur transfection efficiency, induce significant downregulation of the survivin protein, and cause remarkable cell arrest and cell apoptosis. The tube formulation assay demonstrated that SSNs completely disrupted the enclosed capillary networks formed by human microvascular endothelial cells. The in vivo antitumor efficacy showed that SSNs were superior to that of other treatments on drug resistant hepatocellular tumor models. Therefore, it could be an efficient strategy to co-deliver SF and shSur for therapy of drug resistant HCC.

Multidrug resistance (MDR) remains one of the major challenges for successful chemotherapy. Herein, we tried to develope a mitochondria targeted teniposide loaded self-assembled nanocarrier based on stearylamine (SA-TSN) to reverse MDR of breast cancer. SA-TSN was nanometer-sized spherical particles (31.59 ± 3.43 nm) with a high encapsulation efficiency (99.25 ± 0.21%). The MDR in MCF-7/ADR cells was obviously reduced by SA-TSN, which mainly attributed to the markedly reduced expression of P-gp, increased percentages in G2 phase, selectively accumulation in mitochondria, decrease of mitochondrial membrane potential, and greatly improved apoptosis. The plasma concentration of teniposide was greatly improved by SA-TSN, and the intravenously administered SA-TSN could accumulate in the tumor site and penetrate into the inner site of tumor in MCF-7/ADR induced xenografts. In particular, the in vivo tumor inhibitory efficacy of SA-TSN in MCF-7/ADR induced models was more effective than that of teniposide loaded self-assembled nanocarrier without stearylamine (TSN) and teniposide solution (TS), which verified the effectiveness of SA-TSN in reversal of MDR. Thereby, SA-TSN has potential to circumvent the MDR for the chemotherapy of breast cancer.

The endosomal barrier is a major bottleneck for the effective intracellular delivery of siRNA by nonviral nanocarriers. Here, we report a novel amphotericin B (AmB)-loaded, dual pH-responsive micelleplex platform for siRNA delivery. Micelles were self-assembled from poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PDMA-b-PDPA) diblock copolymers. At pH 7.4, AmB was loaded into the hydrophobic PDPA core, and siRNA was complexed with a positively charged PDMA shell to form the micelleplexes. After cellular uptake, the PDMA-b-PDPA/siRNA micelleplexes dissociated in early endosomes to release AmB. Live cell imaging studies demonstrated that released AmB significantly increased the ability of siRNA to overcome the endosomal barrier. Transfection studies showed that AmB-loaded micelleplexes resulted in significant increase in luciferase (Luc) knockdown efficiency over the AmB-free control. The enhanced Luc knockdown efficiency was abolished by bafilomycin A1, a vacuolar ATPase inhibitor that inhibits the acidification of the endocytic organelles. These data support the central hypothesis that membrane poration by AmB and increased endosomal swelling and membrane tension by a “proton sponge” polymer provided a synergistic strategy to disrupt endosomes for improved intracellular delivery of siRNA.

Aim of this study was the site-specific conjugation of an epidermal growth factor (EGF)-polyethylene glycol (PEG) chain by click chemistry onto a poly(amido amine) (PAMAM) dendron, as a key step toward defined multifunctional carriers for targeted gene delivery. For this purpose, at first propargyl amine cored PAMAM dendrons with ester ends were synthesized. The chain terminal ester groups were then modified by oligoamines with different secondary amino densities. The oligoamine-modified PAMAM dendrons were well biocompatible, as demonstrated in cytotoxicity assays. Among the different oligoamine-modified dendrons, PAMAM-pentaethylenehexamine (PEHA) dendron polyplexes displayed the best gene transfer ability. Conjugation of PAMAM-PEHA dendron with PEG spacer was conducted via click reaction, which was performed before amidation with PEHA. The resultant PEG-PAMAM-PEHA copolymer was then coupled with EGF ligand. pDNA transfections in HuH-7 hepatocellular carcinoma cells showed a 10-fold higher efficiency with the polyplexes containing conjugated EGF as compared to the ligand-free ones, demonstrating the concept of ligand targeting. Overall gene transfer efficiencies, however, were moderate, suggesting that additional measures for overcoming subsequent intracellular bottlenecks in delivery have to be taken.

Polypeptide/polysaccharide graft copolymers poly(L-lysine)-graft-chitosan (PLL-g-Chi) were prepared by ring-opening polymerization (ROP) of epsilon-benzoxycarbonyl L-lysine N-carboxyanhydrides (Z-L-lysine NCA) in the presence of 6-O-triphenylmethyl chitosan. The PLL-g-Chi copolymers were thoroughly characterized by 1H NMR, 13C NMR, Fourier transform infrared (FT-IR), and gel permeation chromatography (GPC). The number-average degree of polymerization of PLL grafted onto the chitosan backbone could be adjusted by controlling the feed ratio of NCA to 6-O-triphenylmethyl chitosan. The particle size of the complexes formed from the copolymer and calf thymus DNA was measured by dynamic light scattering (DLS). It was found in the range of 120 approximately 340 nm. The gel retardation electrophoresis showed that the PLL-g-Chi copolymers possessed better plasmid DNA-binding ability than chitosan. The gene transfection effect in HEK 293T cells of the copolymers was evaluated, and the results showed that the gene transfection ability of the copolymer was better than that of chitosan and was dependent on the PLL grafting ratio. The PLL-g-Chi copolymers could be used as effective gene delivery vectors.

Self-assembling of novel biodegradable ABC-type triblock copolymer poly(ethylene glycol)-poly(L-lactide)-poly(L-glutamic acid) (PEG-PLLA-PLGA) is studied. In aqueous media, it self-assembles into a spherical micelle with the hydrophobic PLLA segment in the core and the two hydrophilic segments PEG and PLGA in the shell. With the lengths of PEG and PLLA blocks fixed, the diameter of the micelles depends on the length of the PLGA block and on the volume ratio of H(2)O/dimethylformamide (DMF) in the media. When the PLGA block is long enough, morphology of the self-assembly is pH-dependent. It assembles into the spherical micelle in aqueous media at pH 4.5 and into the connected rod at or below pH 3.2. The critical micelle concentration (cmc) of the copolymer changes accordingly with decreasing solution pH. Both aggregation states can convert to each other at the proper pH value. This reversibility is ascribed to the dissociation and neutralization of the COOH groups in the LGA residues. When the PLGA block is short compared to the PEG or PLLA block, it assembles only into the spherical micelle at various pH values.