Nano Today最新文献

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been developed to treat tumors with potential of clinical applications due to their high spatiotemporal selectivity and non-invasiveness. Nevertheless, the hypoxia within the tumor microenvironment (TME) limits the efficacy of PDT. PTT has the risk of damaging surrounding normal tissues due to the high temperatures essential for killing tumor cells. Herein, we propose a new tumor treatment strategy based on photo-triggered ferroptosis of tumor cells, which is termed photoferroptosis therapy (PFT). The PFT agent (CuS&AIPH@PEG-PAE@PM) was synthesized by encapsulating a radical generator (2,2’-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) and a photothermal agent (copper sulfide, CuS) into an amphiphilic polymer (poly(ethylene glycol)-poly(β-amino ester), PEG-PAE) via self-assembly and a following coating with platelet membrane (PM). Under near-infrared (NIR) irradiation, the PFT agent CuS&AIPH@PEG-PAE@PM generates abundant alkyl radicals (R●) to trigger tumor cell ferroptosis in a moderate temperature and oxygen-independent manner. Meanwhile, the PFT agent also reduces the GSH level and thus suppresses GPX4 expression to promote ferroptosis, which further consolidates the antitumor effect of PFT. The PFT is expected to establish a promising phototherapy strategy against tumors, which has the potential to overcome the limitations of PDT and PTT.

Cancer vaccines have become a milestone in immunotherapy, but inadequate activation rate of antigen presenting cells (APCs) and low delivery efficiency of specific antigen have widely limited their clinical application. Here we design an engineered vaccine platform based on targeted delivery of specific antigens to activated APCs. This vaccine platform is implemented by loading an agonist for stimulator of interferon genes and tumor lysate protein with calcium phosphate as adjuvants, and coating the surface with mannose-modified liposomes. By loading different types of tumor antigen proteins, this nanovaccine platform successfully achieves tumor immunotherapy in breast and colon cancer bearing mice. In addition, personalized nanovaccine prepared from surgically removed tumor lysate proteins also significantly suppresses postsurgical distant tumor. Through the design of nanovaccine platform, we provide an efficient multi-adjuvant delivery platform for multiple types of tumor antigens, and also offer more ideas for personalized vaccine immunization. This nanovaccine platform has great prospects for transformation due to the designability and simplicity for the preparation.

Bioorthogonal reaction refers to chemical reactions that occur within a biological system without interfering the normal biochemical process, offering the unprecedented versatility in engineering chemical reactions within cells. However, the precise regulation of bioorthogonal reaction in living systems is mired by the complexity of the physiological environment and the toxicity of catalysts. Herein, considering the deeper tissue penetration and reduced phototoxicity compared to visible light and ultraviolet, a second near infrared (NIR-II) light-activated Cu-based bioorthogonal reaction is developed to achieve precise spatiotemporal control and effective switching for Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) mediated chemical transformations in tumor, reducing the off-target effects. The catalytic activity of Cu catalyst through valence state interconversion between Cu(II) and Cu(I) can be precisely regulated in a reversible manner under NIR-II light irradiation-induced photoelectron transfer, which controls the extent of desired drug synthesis in bioorthogonal reaction. Meanwhile, the adverse effects of Cu(I) can be substantially mitigated within normal tissues due to their oxygen-rich condition. By utilizing NIR-II light and oxygen level, the Cu bioorthogonal catalyst achieves a balance between catalytic activity and biocompatibility. The ability to achieve precise spatiotemporal control and reversible catalysis makes this NIR-II light-mediated CuAAC platform an efficient and adaptable tool for bioorthogonal chemistry in living systems.

Monolayer-based electronics have emerged as a promising solution that solves the limitations of miniaturization in microelectronic circuits and paves the way for advanced electronic performance applications. Over the past few years, there have been significant advances in monolayer-based electronics from the refinement of fabrication techniques to the elucidation of fundamental mechanisms and the achievement of sophisticated electronic functionalities. In this review, we provide a timely, systematic overview of monolayer-based electronics, covering the preparation processes, charge transport mechanisms, thermoelectric effect, performance regulations, and functional applications. We also offer a detailed summary of devices that leverage either horizontal charge transport or vertical tunneling, along with their respective applications. Furthermore, we delve into the opportunities and challenges inherent in the realm of monolayer- or even single-molecule-based electronics, emphasizing potential breakthroughs that could revolutionize this swiftly evolving domain. Our review aims to provide a broad understanding of monolayer-based electronics and to inspire further research on their practical applications.

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.