Exploration (Beijing, China)最新文献

Because therapeutic cancer vaccines can, in theory, eliminate tumor cells specifically with relatively low toxicity, they have long been considered for application in repressing cancer progression. Traditional cancer vaccines containing a single or a few discrete tumor epitopes have failed in the clinic, possibly due to challenges in epitope selection, target downregulation, cancer cell heterogeneity, tumor microenvironment immunosuppression, or a lack of vaccine immunogenicity. Whole cancer cell or cancer membrane vaccines, which provide a rich source of antigens, are emerging as viable alternatives. Autologous and allogenic cellular cancer vaccines have been evaluated as clinical treatments. Tumor cell membranes (TCMs) are an intriguing antigen source, as they provide membrane-accessible targets and, at the same time, serve as integrated carriers of vaccine adjuvants and other therapeutic agents. This review provides a summary of the properties and technologies for TCM cancer vaccines. Characteristics, categories, mechanisms, and preparation methods are discussed, as are the demonstrable additional benefits derived from combining TCM vaccines with chemotherapy, sonodynamic therapy, phototherapy, and oncolytic viruses. Further research in chemistry, biomedicine, cancer immunology, and bioinformatics to address current drawbacks could facilitate the clinical adoption of TCM vaccines.

Alzheimer's disease (AD) is a debilitating systemic disorder that has a detrimental impact on the overall well-being of individuals. Emerging research suggests that long non-coding RNAs play a role in neural development and function. Nevertheless, the precise relationship between lncRNAs and Alzheimer's disease remains uncertain. The authors' recent discoveries have uncovered an unconventional mechanism involving the regulation of synaptic plasticity and the functioning of the hippocampal fragile X mental retardation protein 1 (FMR1)—neurotrophin 3 (NTF3) pathway, which is mediated by cancer susceptibility candidate 15 (CASC15). Subsequently, functional rescue experiments were performed to illustrate the efficient delivery of exosomes harboring a significant amount of 2610307p16Rik transcripts, which is the murine equivalent of human CASC15, to the hippocampal region of mice. This resulted in significant improvements in synaptic morphological plasticity and cognitive function in APP/PS1 mice. Given the pivotal involvement of CASC15 in synaptic plasticity and the distinctive regulatory mechanisms of the CASC15-FMR1-NTF3 axis, CASC15 emerges as a promising biomarker for Alzheimer's disease and may even possess potential as a feasible therapeutic target.

Photothermal therapy (PTT) has garnered significant attention in recent years, but the standalone application of PTT still faces limitations that hinder its ability to achieve optimal therapeutic outcomes. Nitric oxide (NO), being one of the most extensively studied gaseous molecules, presents itself as a promising complementary candidate for PTT. In response, various nanosystems have been developed to enable the simultaneous utilization of PTT and NO-mediated gas therapy (GT), with the integration of photothermal agents (PTAs) and thermally-sensitive NO donors being the prevailing approach. This combination seeks to leverage the synergistic effects of PTT and GT while mitigating the potential risks associated with gas toxicity through the use of a single laser irradiation. Furthermore, additional internal or external stimuli have been employed to trigger NO release when combined with different types of PTAs, thereby further enhancing therapeutic efficacy. This comprehensive review aims to summarize recent advancements in NO gas-assisted cancer photothermal treatment. It commences by providing an overview of various types of NO donors and precursors, including those sensitive to photothermal, light, ultrasound, reactive oxygen species, and glutathione. These NO donors and precursors are discussed in the context of dual-modal PTT/GT. Subsequently, the incorporation of other treatment modalities such as chemotherapy (CHT), photodynamic therapy (PDT), alkyl radical therapy, radiation therapy, and immunotherapy (IT) in the creation of triple-modal therapeutic nanoplatforms is presented. The review further explores tetra-modal therapies, such as PTT/GT/CHT/PDT, PTT/GT/CHT/chemodynamic therapy (CDT), PTT/GT/PDT/IT, PTT/GT/starvation therapy (ST)/IT, PTT/GT/Ca²⁺ overload/IT, PTT/GT/ferroptosis (FT)/IT, and PTT/GT/CDT/IT. Finally, potential challenges and future perspectives concerning these novel paradigms are discussed. This comprehensive review is anticipated to serve as a valuable resource for future studies focused on the development of innovative photothermal/NO-based cancer nanotheranostics.

Metals are an emerging topic in cancer immunotherapy that have shown great potential in modulating cancer immunity cycle and promoting antitumor immunity by activating the intrinsic immunostimulatory mechanisms which have been identified in recent years. The main challenge of metal-assisted immunotherapy lies in the fact that the free metals as ion forms are easily cleared during circulation, and even cause systemic metal toxicity due to the off-target effects. With the rapid development of nanomedicine, metal-based smart nanosystems (MSNs) with unique controllable structure become one of the most promising delivery carriers to solve the issue, owing to their various endogenous/external stimuli-responsiveness to release free metal ions for metalloimmunotherapy. In this review, the state-of-the-art research progress in metal-related immunotherapy is comprehensively summarized. First, the mainstream mechanisms of MSNs-assisted immunotherapy will be delineated. The immunological effects of certain metals and categorization of MSNs with different characters and compositions are then provided, followed by the representative exemplar applications of MSNs in cancer treatment, and synergistic combination immunotherapy. Finally, we conclude this review with a summary of the remaining challenges associated with MSNs and provide the authors' perspective on their further advances.

Cell membrane-coated nanoparticles (CMNPs) have recently emerged as a promising platform for cancer therapy. By encapsulating therapeutic agents within a cell membrane-derived coating, these nanoparticles combine the advantages of synthetic nanoparticles and natural cell membranes. This review provides a comprehensive overview of the recent advancements in utilizing CMNPs as effective drug delivery vehicles for cancer therapy. The synthesis and fabrication methods of CMNPs are comprehensively discussed. Various techniques, such as extrusion, sonication, and self-assembly, are employed to coat synthetic nanoparticles with cell membranes derived from different cell types. The cell membrane coating enables biocompatibility, reducing the risk of an immune response and enhancing the stability of the nanoparticles in the bloodstream. Moreover, functionalization strategies for CMNPs, primarily chemical modification, genetic engineering, and external stimuli, are highlighted. The presence of specific cell surface markers on the coated membrane allows targeted drug delivery to cancer cells and maximizes therapeutic efficacy. Preclinical studies utilizing CMNPs for cancer therapy demonstrated the successful delivery of various therapeutic agents, such as chemotherapeutic drugs, nucleic acids, and immunotherapeutic agents, using CMNPs. Furthermore, the article explores the future directions and challenges of this technology while offering insights into its clinical potential.

ATP synthase inhibitory factor 1 (ATPIF1), a key modulator of ATP synthase complex activity, has been implicated in various physiological and pathological processes. While its role is established in conditions such as hypoxia, ischemia-reperfusion injury, apoptosis, and cancer, its involvement remains elusive in peripheral nerve regeneration. Leveraging ATPIF1 knockout transgenic mice, this study reveals that the absence of ATPIF1 impedes neural structural reconstruction, leading to delayed sensory and functional recovery. RNA-sequencing unveils a significant attenuation in immune responses following peripheral nerve injury, which attributes to the CCR2/CCL2 signaling axis and results in decreased macrophage infiltration and activation. Importantly, macrophages, not Schwann cells, are identified as key contributors to the delayed Wallerian degeneration in ATPIF1 knockout mice, and affect the overall outcome of peripheral nerve regeneration. These results shed light on the translational potential of ATPIF1 for improving peripheral nerve regeneration.

Recently, the field of nanomedicine has witnessed substantial advancements in the development of nanocarriers for targeted drug delivery, emerges as promising platforms to enhance therapeutic efficacy and minimize adverse effects associated with conventional chemotherapy. Notably, deformable nanocarriers have garnered considerable attention due to their unique capabilities of size changeable, tumor-specific aggregation, stimuli-triggered disintegration, and morphological transformations. These deformable nanocarriers present significant opportunities for revolutionizing drug delivery strategies, by responding to specific stimuli or environmental cues, enabling achieved various functions at the tumor site, including size-shrinkage nanocarriers enhance drug penetration, aggregative nanocarriers enhance retention effect, disintegrating nanocarriers enable controlled drug release, and shape-changing nanocarriers improve cellular uptake, allowing for personalized treatment approaches and combination therapies. This review provides an overview of recent developments and applications of deformable nanocarriers for enhancing tumor therapy, underscores the diverse design strategies employed to create deformable nanocarriers and elucidates their remarkable potential in targeted tumor therapy.

Conductive polymer hydrogels (CPHs) are gaining considerable attention in developing wearable electronics due to their unique combination of high conductivity and softness. However, in the absence of interactions, the incompatibility between hydrophobic conductive polymers (CPs) and hydrophilic polymer networks gives rise to inadequate bonding between CPs and hydrogel matrices, thereby significantly impairing the mechanical and electrical properties of CPHs and constraining their utility in wearable electronic sensors. Therefore, to endow CPHs with good performance, it is necessary to ensure a stable and robust combination between the hydrogel network and CPs. Encouragingly, recent research has demonstrated that incorporating supramolecular interactions into CPHs enhances the polymer network interaction, improving overall CPH performance. However, a comprehensive review focusing on supramolecular CPH (SCPH) for wearable sensing applications is currently lacking. This review provides a summary of the typical supramolecular strategies employed in the development of high-performance CPHs and elucidates the properties of SCPHs that are closely associated with wearable sensors. Moreover, the review discusses the fabrication methods and classification of SCPH sensors, while also exploring the latest application scenarios for SCPH wearable sensors. Finally, it discusses the challenges of SCPH sensors and offers suggestions for future advancements.

Neural interfaces, emerging at the intersection of neurotechnology and urban planning, promise to transform how we interact with our surroundings and communicate. By recording and decoding neural signals, these interfaces facilitate direct connections between the brain and external devices, enabling seamless information exchange and shared experiences. Nevertheless, their development is challenged by complexities in materials science, electrochemistry, and algorithmic design. Electrophysiological crosstalk and the mismatch between electrode rigidity and tissue flexibility further complicate signal fidelity and biocompatibility. Recent closed-loop brain-computer interfaces, while promising for mood regulation and cognitive enhancement, are limited by decoding accuracy and the adaptability of user interfaces. This perspective outlines these challenges and discusses the progress in neural interfaces, contrasting non-invasive and invasive approaches, and explores the dynamics between stimulation and direct interfacing. Emphasis is placed on applications beyond healthcare, highlighting the need for implantable interfaces with high-resolution recording and stimulation capabilities.

Snap-through bistability was widely exploited for rapid hopping in micro-electro-mechanical systems and soft robots. However, considerable energy input was required to trigger the transition between discrete buckling states blocked by potential wells. Here a dynamic buckling mechanism of a buckled blister constrained inside an outer ring is explored for eliciting rotary actuation via a localized change of curvature in the blister. Due to rotational invariance of the buckled blister, lower energy supply is required to initiate the snap-through of buckling compared to conventional bistable mechanism. The controllability in rotational speed and output torque of the bimetallic blister-based rotator inside a rigid stator is exhibited, and the locomotion is demonstrated with two elastic rings via localized pneumatic actuators. With broad choices of stimulus and material for rings, the findings illustrate the promising potential of two nested rings to create active motions for diverse applications including gearless motors, peristaltic pumps, and locomotive robots.