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 transgenicmice, 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 theCCR2/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.

Infected burn wounds are characterized by persistent drug-resistant bacterial infection coupled with an inflammatory response, impeding the wound-healing process. In this study, an intelligent nanoparticle system (CCM+TTD@ZIF-8 NPs) was prepared using curcumin (CCM), an aggregation-induced emission luminogens (TTD), and ZIF-8 for infection-induced wound healing. The CCM+TTD@ZIF-8 NPs showed multiple functions, including bacteria targeting, fluorescence imaging and pH response-guided photodynamic therapy (PDT), and anti-inflammatory. The positive charges of ZIF-8 NPs allowed the targeting of drug-resistant bacteria in infected wounds, thereby realizing fluorescence imaging of bacteria by emitting red fluorescence at the infected site upon blue light irradiation. The pH-responsive characteristics of the CCM+TTD@ZIF- 8 NPs also enabled controllable CCM release onto the infected wound site, thereby promoting the specific accumulation of ROS at the infected site, with outstanding bactericidal efficacy against drug-resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) strains in vitro/in vivo. Additionally, due to the excellent bactericidal effect and anti-inflammatory properties of CCM+TTD@ZIF-8 NPs combined with blue light irradiation, the regeneration of epidermal tissue, angiogenesis, and collagen deposition was achieved, accelerating the healing process of infected burn wounds. Therefore, this CCM+TTD@ZIF-8 NPs with multifunctional properties provides great potential for infected burn wound healing.

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.

Over the last two decades, lipid nanoparticles (LNPs) have evolved as an effective biocompatible and biodegradable RNA delivery platform in the fields of nanomedicine, biotechnology, and drug delivery. They are novel bionanomaterials that can be used to encapsulate a wide range of biomolecules, such as mRNA, as demonstrated by the current successes of COVID-19 mRNA vaccines. Therefore, it is important to provide a perspective on LNPs for RNA delivery, which further offers useful guidance for researchers who want to work in the RNA-based LNP field. This perspective first summarizes the approaches for the preparation of LNPs, followed by the introduction of the key characterization parameters. Then, the in vitro cell experiments to study LNP performance, including cell selection, cell viability, cellular association/uptake, endosomal escape, and their efficacy, were summarized. Finally, the in vivo animal experiments in the aspects of animal selection, administration, dosing and safety, and their therapeutic efficacy were discussed. The authors hope this perspective can offer valuable guidance to researchers who enter the field of RNA-based LNPs and help them understand the crucial parameters that RNA-based LNPs demand.

Immunomodulation has emerged as a promising strategy for promoting bone regeneration. However, designing osteoimmunomodulatory biomaterial that can respond to mechanical stress in the unique microenvironment of alveolar bone under continuous occlusal stress remains a significant challenge. Herein, a wireless piezoelectric stimulation system, namely, piezoelectric hydrogel incorporating BaTiO₃ nanoparticles (BTO NPs), is successfully developed to generate piezoelectric potentials for modulating macrophage reprogramming. The piezoelectric stimulation reprograms macrophages towards theM2 phenotype, which subsequently induces osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RNA sequencing analysis reveals that piezoelectricity-modulated macrophage M2 polarization is closely associated with metabolic reprogramming, including increased amino acid biosynthesis and fatty acid oxidation. The composite hydrogel with excellent biocompatibility exhibits immunomodulatory and osteoinductive activities. In a rat model of alveolar bone defects, the piezoelectric hydrogel effectively promotes endogenous bone regeneration at the load-bearing sites. The piezoelectric-driven osteoimmunomodulation proposed in this study not only broadens understanding of the mechanism underlying piezoelectric biomaterials for tissue regeneration but also provides new insights into the design and development of next-generation immunomodulatory biomaterials.

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 forAlzheimer’s disease andmay 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 dualmodal 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.

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.

Recently, biomass-derived carbon dots (CDs) have attracted considerable attention in high-technology fields due to their prominent merits, including brilliant luminescence, superior biocompatibility, and lowtoxicity.However, most of the biomass-derived CDs only show bright fluorescence in diluted solution because of aggregation-induced quenching effect, hence cannot exhibit solid-state long-lived room-temperature phosphorescence (RTP) in ambient conditions. Herein, matrix-free solid-state RTP with an average lifetime of 0.50 s is realized in the CDs synthesized by one-pot hydrothermal treatment of duck feather waste powder. To further enhance RTP lifetime, hydrogen bonding is introduced by employing polyols like polyvinyl alcohol (PVA) and phytic acid (PA), and a bimodal luminescent CDs/PVA/PA ink is exploited by mixing the CDs and polyols. Astonishingly, the CDs/PVA/PA ink screen-printed onto cellulosic substrates exhibits unprecedented green RTP with average lifetime of up to 1.97 s, and the afterglow lasts for more than 14 s after removing UV lamp. Such improvement on RTP is proposed to the populated excited triplet excitons stabilized by rigid chains. Furthermore, the CDs/PVA/PA ink demonstrates excellent potential in anticounterfeiting and information encryption. To the best of the authors’ knowledge, this work is the first successful attempt to fabricatematrix-free ultra-long RTP CDs by reclamation of the feather wastes for environmental sustainability.

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 providemembrane-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 preparationmethods are discussed, as are the demonstrable additional benefits derived fromcombining TCMvaccines 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.

Treating brain tumors requires a nuanced understanding of the brain, a vital and delicate organ. Location, size, tumor type, and surrounding tissue health are crucial in developing treatment plans. This review comprehensively summarizes various treatment options that are available or could be potentially available for brain tumors, including physical therapies (radiotherapy, ablation therapy, photodynamic therapy, tumor-treating field therapy, and cold atmospheric plasma therapy) and non-physical therapies (surgical resection, chemotherapy, targeted therapy, and immunotherapy). Mechanisms of action, potential side effects, indications, and latest developments, as well as their limitations, are highlighted. Furthermore, the requirements for personalized, multi-modal treatment approaches in this rapidly evolving field are discussed, emphasizing the balance between efficacy and patient safety.

High expression of cellular self-activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma’s resistance to immunotherapy. Nonetheless, technology to modify the expression of glioma cellular self-molecules through gene editing requires further development. This project advances cell therapy strategies to reverse the immunosuppressive microenvironment of glioma (TIME). Bone marrow-derived mesenchymal stem cells (MSCs) are engineered to express bioactive proteins and demonstrate tumor-homing characteristics upon activation by TGF-β. TheseMSCs are designed to secrete the anti-tumor immune cytokine IL-12 and the nCD47-SLAMF7 fusion protein, which regulates T-cell activity and macrophage phagocytosis. The engineered MSCs are then injected in situ into the glioma site, circumventing the blood-brain barrier to deliver high local concentrations of bioactive proteins. This approach aims to enhance the M1 polarization of infiltrating macrophages, stimulate macrophage-mediated tumor cell phagocytosis, activate antigen-presenting cells, and promote effector CD8⁺ T cell infiltration, effectively controlling glioma. Additionally, the engineered MSCs may serve as a universal treatment for other tumors that express TGF-β at high levels. This study proposes a novel treatment strategy for the clinical management of glioma patients.