Nano Today最新文献

Mitochondria are essential for maintaining cellular survival and function, and their dysfunction is implicated in cancer, cardiovascular abnormalities, neurodegenerative diseases, aging, and so on, carrying significant pathophysiological implications. Conducting research focused on mitochondria helps elucidate the mechanisms of disease development and offers new therapeutic perspectives for combating challenging conditions like malignant tumors, myocardial injury, Parkinson's disease, and other related ailment. In recent years, the flourishing development of near-infrared (NIR) technology has provided powerful tools for mitochondrial research. NIR light serves as both an information carrier for biological imaging and analysis, and as a non-invasive stimulus in drug delivery, phototherapy, and energy conversion applications. Currently, a large number of NIR materials have been applied to target mitochondria in disease diagnosis, treatment, and theranostics. These materials have garnered significant attention due to their unique properties and remarkable in vivo performance. This review aims to provide researchers developing mitochondria-targeted NIR materials for biomedical applications with an advanced and comprehensive guide. It not only offers valuable insights into design strategies, material properties, and applications in disease diagnosis and treatment, such as strategies to improve imaging sensitivity, specificity, and therapeutic efficacy, but also delves into the existing challenges in the field, issues that persist in clinical translation, and future prospects.

Achieving efficient and secure cytosolic delivery is crucial for RNA therapeutics. Presently, delivery systems predominantly attain cytosolic release through membrane rupture or destabilization of late endosomes and lysosomes. However, these approaches lead to restricted RNA release and undesirable cytotoxicity, ultimately diminishing therapeutic efficacy. Herein, we proposed an efficient strategy based on early endosome fusion-mediated release, employing probiotic-derived lipopolysaccharide (LPS)-incorporated vesicles to enhance RNA delivery. The LPS is derived from Escherichia coli Nissle 1917 (EcN) and has a high safety confirmed by the authoritative pyrogen test. The LPS-rich outer membrane vesicles (OMVs) and synthetic chimeric liposomes (LPS-Lips) are found capable of efficient cytosolic RNA delivery by using LPS to fuse with early endosomes, as evidenced by super-resolution and real-time imaging. The OMVs and LPS-Lips (containing 10 % and 30 % EcN-derived LPS) exhibit enhanced ability to deliver functional BCL-xL siRNA, leading to more significant gene silencing and cell apoptosis in comparison to the commercial Lipofectamine 2000 and RNAiMAX groups. The in vivo results demonstrate their superior efficacy on inhibiting tumor growth and prolonged survival time with enhanced safety. These findings highlight the early endosome fusion strategy with facilitated release efficiency and safety, offering guidelines for the rational design of enhanced RNA delivery systems.

Immunotherapy for advanced colorectal cancer has made the considerable progress. However, the most patients have unsatisfactory immune response due to immunosuppressive tumor microenvironment (TME). We construct a hyaluronic acid (HA) functionalized nanoplatform (MnOx@MIL-100@CDDP@HA, MMCH) with MnOx as core and MIL-100 as shell for loading cisplatin to boost the antitumor immune response by the synergistic effect of activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and ferroptosis-induced immunogenic cell death. MMCH could achieve the TME-responsive CDDP release and alleviating tumor hypoxia, which effectively increased the damage of nuclear DNA (nDNA) to improve the efficacy of chemotherapy. The abilities of consuming GSH and producing ·OH of MMCH could cause ferroptosis, further induced immunogenic cell death (ICD), result in boosting an adaptive immune response. The generated ROS and CDDP caused damage to nDNA and mitochondrial DNA (mitoDNA), and further initiated the cGAS-STING pathway to trigger innate immune, which could be enhanced by Mn²⁺ via improving sensitivity of cGAS to dsDNA. The activation of adaptive and innate immune response could result in an excellent antitumor immunity response and long-lasting immunological memory, remarkably impede primary tumor growth and relapse in vitro and vivo. Therefore, this strategy of provoking cGAS-STING pathway and inducing ferroptosis has a promising potential to induce adaptive and innate immune response for boosting colorectal cancer immunotherapy.

We report a diatomic-site catalyst configuration constituted by Ni-N₃ and Bi-N₄ embedded in ultrathin nitrogenated carbon nanosheets (Ni/Bi-N-C) which showed dramatically improved activity and selectivity for the conversion of CO₂ to CO. Specifically, the catalyst exhibited high CO Faradaic efficiency (FE_CO) of above 90 % over a wide potential window from −0.76 to −2.22 versus reversible hydrogen electrode with the maximum CO partial current density up to 312 mA cm⁻² in a flow cell, and coupled with robust durability. Ni/Bi-N-C-based membrane electrode assembly (MEA) device presented ultrahigh FE_CO of 95.7 % at 750 mA and over 100 h of continuous operation without decay under constant current density of 100 mA cm⁻². Mechanistic studies and density functional theory calculations reveal that regulating the CO₂RR catalytic performance via nearby Ni and Bi active sites can potentially break the activity benchmark of the single metal counterparts because the neighboring Ni and Bi active sites work in synergy to decrease the reaction barrier for the formation of *COOH and desorption of *CO. This work presents an efficient combination of two metal atomic sites which was designed by optimizing the interaction between the atomic sites and key reaction intermediates, resulting in the high-rate electrocatalytic CO₂ reduction.

Viruses transmitted through the respiratory tract tend to have short incubation periods and are highly contagious, thus being one of the main triggers of acute respiratory illnesses. Vaccines are important tools for reducing viral infections and preventing serious illness, hospitalization, and death. However, vaccines are still not widely accessible in some areas, particularly in low-income countries, because of limited production capacity and inadequate medical personnel, resulting in high morbidity and mortality rates during pandemics. Therefore, there is an urgent need for the development of vaccines that can be rapidly manufactured and self-administered in response to pandemics caused by respiratory-transmitted viruses. In this work, we developed an inhalable vaccine platform consisting of antigen-engineered cell membrane vesicles (CMVs) and cholesterolized CpG anchoring to the vesicle surface to establish an “all-in-one” vaccine platform (antigen/CpG-CMVs), which could induce mucosal immunity upon oropharyngeal inhalation to protect against viral infections in the respiratory tract. Its antigen, adjuvant, and particle size can be adjusted as needed through gene editing, cholesterol modification, and extrusion process, respectively. The lyophilized antigen/CpG-CMVs can be distributed without cold-chain transportation and can be self-administered by inhalation upon reconstitution. We found that this inhalable “all-in-one” vaccine induced not only systemic immunity but also mucosal immunity in the respiratory tract, as reflected by the enhanced levels of systemic immunoglobulin G (IgG) and respiratory secreted immunoglobulin A (sIgA). This work may validate engineered cell membrane vesicles as an inhalable vaccine platform and a promising avenue for future vaccine development to protect against pandemics.

The widespread prevalence of antifungal resistance results in the ineffective treatment of Candida-related infections since current approaches still heavily rely on antifungal drugs such as azoles. Adjuvant therapy is an alternative approach to alleviate this crisis that can re-sensitize multidrug-resistant (MDR) fungi to antifungal drugs. Herein, we report a synergistic strategy to restore antifungal activity of azoles against MDR Candida albicans (C. albicans) through nanotechnology. C. albicans-mediated biosynthetic gold nanoparticles (Ca_AuNPs) exhibit a significant potentiating effect (16–32 folds) on azoles (including fluconazole, itraconazole, and voriconazole) against MDR C. albicans. Mechanistic studies demonstrate that Ca_AuNPs can promote the intracellular accumulation of fluconazole and trigger the biochemical processes including cell structure destruction, membrane potential dissipation, intracellular ROS generation, and ATP level reduction to overcome the fungal intrinsic resistance. We demonstrate that the adjuvant therapy significantly reduces fungal viability and enhances vaginal mucosa regeneration when treating Candida vaginitis-infected mice. This study reveals the potential of biosynthetic nanoparticles as novel adjuvants to extend the lifespan of existing antifungal drugs for the treatment of MDR pathogen-induced infections.

2D/3D perovskite heterojunctions typically yield mixed-phase 2D perovskites, generating multiple quantum wells that impede charge transfer, thereby limiting the potential enhancement of solar cell efficiency. Here, we successfully fabricated phase-pure 2D (n = 2)/3D perovskite heterojunctions via introducing the γ-aminobutyric acid (GABA) ligand, which minimized energetic inhomogeneity, thus favoring interfacial charge transfer through optimized energy band alignment. The ligation between the oxygen atoms in the ligand and the uncoordinated lead in the 3D perovskite triggered a structural transition from cubic to tetragonal at the 3D perovskite surface, ensuring a seamless lattice matching with the 2D perovskite (n = 2), resulting in this optimized configuration. Utilizing this innovative structural configuration, the carrier properties of 2D/3D perovskite thin films have been significantly enhanced, exhibiting diffusion lengths exceeding 1000 nm and a mobility of 3.35 cm² V⁻¹ s⁻¹. Consequently, the fabricated small-area perovskite solar cells exhibited an impressive power conversion efficiency (PCE) of 25.06 %, while the mini-modules (10 cm × 10 cm) attained a maximum PCE of 17.27 %. Furthermore, the passivation of the 2D perovskite layers, coupled with their inherent superior resistance, enabled the unencapsulated target device to maintain outstanding long-term stability, even under challenging environmental conditions of light, heat, and humidity.

Niobium is attracting more and more attention in dental and orthopedic clinical applications. On the one hand, niobium alloy has verified its good biocompatibility, corrosion resistance and mechanical properties; on the other hand, niobium nanomaterials could reduce the osteoclast activation through ROS absorption, which is conducive to bone tissue regeneration. The impressive osteogenesis ability of niobium-based nanomaterials inspired the strategy to load the 2D niobium into bioactive responsive carriers and directly deploy in bone defects to promote bone regeneration efficiently and in situ. Here, a bone cement was constructed through the innovative super-assembled strategy that had integrated the nano-level 2D niobium carbide MXene to the macroscopic 3D GelMA photo-cured frameworks. The super-assembled bone cement can achieve accelerated bone fracture healing and osseointegration in various preclinical mouse models without any detectable toxicity. Mechanistically, 2D Nb₂C bone cement promoted osteoblast activation without altering osteoclast function in vivo. Transcriptomics and chromatin immunoprecipitation revealed that 2D Nb₂C stimulates GATA3-GPNMB signaling to active osteoblasts in mice. In freshly isolated human osteoblasts, 2D Nb₂C stimulated osteoblast activation and calcification. This work proposes a topically effective, non-toxic, low-cost 2D Nb₂C-based bone cement with distinct clinical translational potential in dentistry and orthopedics.

Acute myeloid leukemia (AML) is a rapidly proliferating blood cancer, necessitating treatments that specifically target and swiftly eradicate it. In this study, we develop an AML-specific, apoptotic cell death-inducing protein nanoparticle, AaLS/TRAIL/aCD13Nb, by simultaneously displaying multiple CD13-binding nanobodies (aCD13Nb) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) molecules on a single AaLS protein nanoparticle using the SpyCatcher/SpyTag protein ligation system. AaLS/TRAIL/aCD13Nb selectively binds to various CD13-overexpressing AML cell lines and effectively accumulates near U937 AML tumor sites through systemic administration, demonstrating its AML targeting capabilities. The tight binding of AaLS/TRAIL/aCD13Nb to CD13-overexpressing AML cells, mediated by aCD13Nb, results in close and continuous contact between TRAIL molecules and death receptors, triggering robust apoptotic cell death. Systemic administrations of AaLS/TRAIL/aCD13Nb into U937 AML-engrafted NSG mice significantly reduce the AML burden and nearly double the mice’s survival period, especially under advanced and severe AML conditions. Collectively, our study paves the way for targeted therapies in AML, utilizing protein nanoparticles as nanoplatforms. Substantial therapeutic efficacy across various cancers can be achieved by strategically combining cancer-specific targeting ligands with apoptotic cancer cell death-inducing molecules, tailored to specific cancer types.

Flexible sensors simultaneously with property of hydrogel-like low modulus/room temperature ultra-fast self-healing and with elastomer-like durability /environmental stability and underwater adhesion for bioelectronics has not been reported. A low modulus hydrogel-like elastomer that achieves ultrafast self-healing through molecular chain entanglement at room temperature was prepared based on furfuryl alcohol-modified poly(sebacate glyceride) (PGS) prepolymer, furfuryl alcohol-modified poly(ionic liquid) and bismaleimide by Diels-Alder (DA) reaction. The conductive elastomer-based flexible sensors exhibit hydrogel-like properties of low modulus (6.41 kPa) and ultra-fast self-healing (98 % self-healing efficiency within 5 s). The elastomer also possesses rapid subzero and underwater self-healing properties within 5 s. Moreover, PGS-0.2DA-0.2PIL exhibits pressure sensitive adhesive properties and can be adhered/re-adhered in water. The flexible sensor shows elastomer-like high durability, high environmental stability, multiple recyclability and reusability, and it exhibits wide detection ranges, fast response time, low hysteresis, anti-freezing, anti-bacterial and good biocompatibility. The flexible sensors can accurately identify micro-expressions/eye rotation, monitor human movement/health, detect ECG/EMG signals and control robotic arm movements. In conclusion, a new strategy for design of hydrogel-like conductive elastomers via molecular structure design is proposed, and the elastomers-based flexible sensors with low modulus, rapid self-healing and durability/environmental stability show great promising for bioelectronic applications.