Rationalized landscape on protein-based cancer nanomedicine: Recent progress and challenges.

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

VRK1 promotes DNA-induced type I interferon production.

BACKGROUND: Type I interferons (IFNs) are an essential class of cytokines with antitumor, antiviral and immunoregulatory effects. However, over-productive the type I IFNs are tightly associated with autoimmune disorders. Thus, the induction of type I interferons is precisely regulated to maintain immune hemostasis. This study aimed to identify a novel regulator of type I interferon signaling. METHODS AND RESULTS: Primary BMDMs, isolated from mice, and human cell lines (HEK293 cells, Hela cells) and murine cell line (MEF cells) were cultured to generate in vitro models. After knockdown VRK1, real-time PCR and dual-luciferase reporter assay were performed to determine the expression level of the type I IFNs and ISGs following HTDNA and Poly (dA:dT) stimulation. Additionally, cells were treated with the VRK1 inhibitor, and the impact of VRK1 inhibition was detected. Upon HTDNA and Poly (dA:dT) stimulation, knockdown of VRK1 attenuated the induction of the type I IFNs and ISGs. Consistently, VRK-IN-1, a potent and selective VRK1 inhibitor, significantly suppressed the induction of the type I IFNs and ISGs in human and murine cell lines. Further, VRK-IN-1 inhibited induction of the type I IFNs in mouse primary BMDMs. Intriguingly, VRK1 potentiated the cGAS-STING- IFN-I axis response at STING level. CONCLUSIONS: Our study reveals a novel function of VRK1 in regulating the production of type I IFNs. VRK-IN-1 might be a potential lead compound for suppressing aberrant type I IFNs in autoimmune disorders.

UPLC-Q-TOF/MS based metabolite profiling and quality marker constituents screening of root, stem and rhizome extracts of Ilex asprella.

OBJECTIVE: The root of Ilex asprella (RIA) is a popular plant resource for treating inflammation-related diseases. The purpose of this study was to identify the secondary metabolites, to compare anti-inflammatory effects and to determine the quality marker components among root, stem and rhizome sections of IA. METHODS: Chemical fingerprints of stem, root and rhizome of IA was determined by high performance liquid chromatography (HPLC). A reliable method using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for comprehensively determining the chemical constituents of the plants. Anti-inflammatory activities of IA and its ingredients were screened by in vivo mouse ear swelling and in vitro LPS-induced release of NO from RAW264.7 cells experiments. RESULTS: Root, stem and rhizome of IA have shown high similarity in chemical fingerprints. Totally 149 compounds were characterized in IA, including triterpenoids, triterpenoid saponins, phenolic acids and lignans. 44 of them were identified based on co-occurring Mass2Motifs, including 19 unreported ones, whilst 17 were tentatively confirmed by comparison with reference compounds. No significant anti-inflammatory activity difference among root, stem and rhizome parts of IA was found. Ilexsaponin B2, protocatechualdehyde, isochlorogenic acid B and quinic acid, were screened out as quality marker compounds in IA. CONCLUSION: A sensitive and rapid strategy was established to evaluate the differences on secondary metabolites of different parts of IA for the first time, and this study may contribute to the quality evaluation of medicinal herbs and provide theoretically data support for further analysis of different parts of IA.

A mesoporous Al2O3 zincophilic sieve enables ultra-long lifespan of Zn-ion batteries.

The Zn dendrite growth and side reactions hinder the practical application of aqueous Zn-ion batteries. Here, a lactic acid-induced mesoporous Al2O3 (LA-MA) zincophilic sieve was constructed on a Zn anode to resolve these issues. The LA-MA layer with abundant mesoporous ion channels of 3.0 nm can regulate the solvation structure from [Zn2+(H2O)6]SO42- to more highly coordinated [Zn2+(H2O)5OSO32-] and restrain water-induced side reactions. Furthermore, the electrostatic attraction with zincophilic groups (CO, C-O) in the LA-MA layer has a positive effect on reducing the Zn2+ desolvation barrier and accelerating the Zn2+ diffusion. Under the synergism, the LA-MA@Zn symmetric cell exhibits over 5100 h at 0.25 mA cm-2. Impressively, an excellent capacity retention of 94.2% is achieved after 3500 cycles for the CNT/MnO2 cathode.

Stable Plating and Stripping of Lithium Metal Anodes through Space Confinement and Stress Regulation.

Lithium metal anodes suffer from enormous mechanical stress derived from volume changes during electrochemical plating and stripping. The utilization of derived stress has the potential for the dendrite-free deposition and electrochemical reversibility of lithium metal. Here, we investigated the plating and stripping process of lithium metal held within a cellular three-dimensional graphene skeleton decorated with homogeneous Ag nanoparticles. Owing to appropriate reduction-splitting and electrostatic interaction of nitrogen dopants, the cellular skeletons show micron-level pores and superior elastic property. As lithium hosts, the cellular skeletons can physically confine the metal deposition and provide continuous volume-derived stress between Li and collectors, thus meliorating the stress-regulated Li morphology and improving the reversibility of Li metal anodes. Consequently, the symmetrical batteries exhibit a stable cycling performance with a span life of more than 1900 h. Full batteries (NCM811 as cathodes) achieve a reversible capacity of 181 mA h g-1 at 0.5 C and a stable cycling performance of 300 cycles with a capacity retention of 83.5%. The meliorative behavior of lithium metal within the cellular skeletons suggests the advantage of a stress-regulating strategy, which could also be meaningful for other conversion electrodes with volume fluctuation.

Charge reversal hairpin peptide modified synergy therapeutic nanoplatforms for tumor specific drug shuttling.

Given the distinct pathological features of neoplasm tissues, multifunctional responsive nanocarriers have been recently considered as promising candidates to optimize the chemotherapy regime. As a result, we propose a graphene oxide-based pH-responsive drug delivery system via covalent assembly of "hairpin-like" cell penetrating peptides with acid sensitive and charge reversal properties to realize superior tumor specificity and lower toxicity. Graphene oxide here can serve as high doxorubicin-loading nanosheets and facilitate swift drug release in response to laser irradiation, which provides an efficient platform for the synergy of photo-chemotherapy. Structurally, polyglycol conjugation on the graphene oxide surface fulfils the function of nanocomposite stabilization. After administration, the elaborately acid sensitive cell penetrating peptides maintain the hairpin structure under physiological conditions, while after entering the tumor acidic microenvironment, they undergo charge reversal and structural conversion to promote the cellular uptake of nanoparticles. The evaluation of nanocomposites in vitro revealed their negligible systematic toxicity and remarkable antitumor effects. In vivo experiments also confirmed the impressive stability and tumor-specific targeting for alleviating breast cancer. In conclusion, hairpin peptide modified graphene oxide nanoparticles show multiple merits including high drug carrying capacity, selective tumor penetration, responsive drug release and effective combination oncotherapy.

Synergistic Catalysis by Single-Atom Catalysts and Redox Mediator to Improve Lithium-Oxygen Batteries Performance.

Lithium-oxygen (Li-O2 ) batteries with ultrahigh theoretical energy density have attracted widespread attention while there are still problems with high overpotential and poor cycle stability. Rational design and application of efficient catalysts to improve the performance of Li-O2 batteries is of significant importance. In this work, Co single atoms catalysts are successfully combined with redox mediator (lithium bromide [LiBr]) to synergistically catalyze electrochemical reactions in Li-O2 batteries. Single-atom cobalt anchored in porous N-doped hollow carbon spheres (CoSAs-NHCS) with high specific surface area and high catalytic activity are utilized as cathode material. However, the potential performances of batteries are difficult to adequately achieve with only CoSAs-NHCS, owing to the blocked electrochemical active sites covered by insulating solid-state discharge product Li2 O2 . Combined with LiBr as redox mediator, the enhanced OER catalytic effect extends throughout all formed Li2 O2 during discharge. Meantime, the certain adsorption effect of CoSAs-NHCS on Br2 and Br3 - can reduce the shuttle of RMox . The synergistic effect of Co single atoms and LiBr can not only promote more Li2 O2 decomposition but also reduce the shuttle effect by absorbing the oxidized redox mediator. Li-O2 batteries with Co single atoms and LiBr achieve ultralow overpotential of 0.69 V and longtime stable cyclability.