Nano Today最新文献

Constructing the coordination environment of single-atom catalysts (SACs) can be an attractive technical strategy to regulate the generation of reactive oxygen species for Fenton-like reactions. Herein, we have constructed an asymmetric coordination of Fe single-atom catalyst (Fe_SA-NS-PCNS) with abundant N-Fe-S bridge (Fe_SA-N₃S₁) for robust Fenton-like reactions. 82.5 % of singlet oxygen (¹O₂) selectivity and high turnover frequency of bisphenol A degradation (0.568 min⁻¹) were achieved at mild conditions. Experimental works and theoretical analyses illustrated that S doping breaks the inert environment of the original N-Fe-N symmetric coordination equilibrium and modulates the electron density of the atomic Fe center, which is beneficial for boosting PMS adsorption and reducing the energy barriers of vital *OH and *O intermediates. The coupling between the Fe_SA-N₃S₁ interface and peroxymonosulfate molecule boosts in-situ electron transfer through the N-Fe-S bridge, which induces more electron flow from the low valence Fe to OH* on the surface of Fe-*O-H, forming a high yield of ¹O₂. Moreover, we designed the Fenton-like reactions by Fe_SA-NS-PCNS membrane reactor for an efficient contaminant removal rate of over 90 % even after 11 cycles. This work provides a novel perspective on developing SACs with asymmetric coordination to regulate reactive oxygen species for the treatment of organic contaminants in water bodies.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, as an important part in innate immunity, has recently emerged as a promising target for improving tumor therapy. Manganese ions (Mn²⁺) are an emerging agonist in the cGAS-STING pathway with multifaceted advantages, however manganese-based nanoparticles alone as the Mn²⁺ source have shown limited activity in eliciting anti-tumor immune responses compared to conventional organic STING agonists, and the underlying mechanism of the suboptimal efficiency remains unclear. Here, we demonstrate that intratumoral iron ions attenuate manganese-induced anti-tumor STING activation, and that the utilization of deferoxamine (DFO), an iron chelator that depletes intratumoral iron ions, effectively increases the intracellular accumulation of Mn²⁺ and thus promoted the STING activation efficiency of a hyaluronic acid modified manganese carbonate-silica hybrid nanoparticle (DS@Mn-H) in macrophages. The mechanism study suggests that the addition of DFO inhibited the expression of ferroportin (FPN), which serves as a Mn²⁺ exporter to reduce intracellular Mn²⁺ level. The synergistic effect of DS@Mn-H and DFO achieved excellent anti-tumor activities in a mouse colon carcinoma model. This work provides new insights on improving the Mn-based metallo-immunotherapy of cancer.

Immunosuppressive tumor microenvironment and inadequate activation of the innate immune system are important reasons for the failure of systemic anti-tumor immunotherapy. Irradiated tumor cell-derived microparticles (RMPs) can induce immunogenic cell death (ICD) of tumor cells and inhibit the M2-like phenotype of tumor-associated macrophages (TAMs). The current study found that double-stranded DNA was enriched in RMPs, which combined with manganese ions (Mn²⁺), the natural activator of cGAS-STING signaling, and synergistically amplified cGAS-STING signaling cascade in antigen-presenting cells (APCs). On this basis, a polyamino acid thermosensitive hydrogel delivery system was designed to simultaneously load RMPs and Mn²⁺. The obtained RMPs@Mn²⁺ hydrogel exhibited thermosensitivity, biocompatibility and sustained release characteristics. The intratumoral injection of RMPs@Mn²⁺ slowly released RMPs and Mn²⁺, inducing ICD of tumor cells, continuously activating cGAS-STING signaling of APCs, reprograming TAMs to M1-like phenotype, and promoting the activation of dendritic cells in tumor draining lymph nodes. The full activation of innate immunity at the tumor site further promoted priming and tumor infiltration of T cells, leading to tumor regression. RMPs@Mn²⁺ combined with anti-PD-1 achieved strong anti-cancer efficacy in a refractory malignant ascites model, in which more than 50 % of mice with malignant ascites achieved complete regression and long-term immune memory.

The commercial success of hydrogen (H₂) production via seawater electrolysis largely depends on overcoming anode corrosion caused by chloride (Cl⁻), a critical challenge for scaling up renewable energy storage. Herein, we present the synthesis of nickel hexacyanoferrate Prussian blue analogues via anodic polarization for efficient alkaline seawater oxidation (ASO). Electrochemical experiments and in situ Raman studies unveil that leaching of Fe(CN)₆³⁻ from the electrode facilitates a dynamic self-reconstruction process and leads to the formation of high-valence metal reaction specie, and appropriate Fe(CN)₆³⁻ effectively shields active sites from Cl⁻ interference even at ampere-level current density (j). In experiments, our electrode demonstrates an overpotential of merely 349 mV to reach a j of 1 A cm⁻² and maintains stable operation for over 1000 h with protective Fe(CN)₆³⁻. This work showcases the potential of Prussian blue analogues for efficient and long-lasting ASO, protecting against Cl⁻ in large-scale seawater H₂ electrolysis.

Oxidative stress significantly contributes to various ocular diseases, necessitating innovative therapeutic approaches. This manuscript explores nanozymes which are nanomaterials with enzyme-like activities, as potential therapeutic agents for oxidative stress-related eye diseases. The rising global incidence of visual impairments underscores the urgent requirement for effective, adaptable, and safe therapeutic options. We detail how oxidative stress damages ocular tissues, the limitations of natural antioxidants, and discuss the benefits of nanozymes, such as their stability, multi-enzyme activity, and enhanced drug delivery capabilities. Our review covers nanozyme applications in various eye diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, optic neuritis, cataracts, dry eye syndrome, chemical corneal burns, and uveitis. We also explore innovative delivery methods, such as microneedles, contact lenses, and hydrogels, which can enhance the bioavailability and therapeutic efficacy of nanozymes. The manuscript concludes by emphasizing the existing limitations and the promising future of nanozymes in ocular antioxidant therapy. With their multi-enzyme activity and improved delivery systems, nanozymes represent a significant advancement over traditional treatments, offering new hope for managing and potentially curing various oxidative stress-related eye diseases.

Immune checkpoint blockade (ICB) has shown great promise in the management of various cancers. However, only a small percentage of patients profit from ICB therapy. Immunogenic cell death (ICD) has demonstrated its specific capability in reconstructing the tumor microenvironment (TME) and activating anti-tumor immunity. Herein, an ICD cascade enhancement based on BPTL nanoreactors is proposed to overcome the inadequate damage-associated molecular patterns of ICD inducers. BPTL nanoreactor is formed by incorporating the piezocatalytic BaTiO₃ (T-BTO) nanoparticles and paclitaxel (PTX) prodrug that responds to reactive oxygen species (ROS) into liposome nanoparticles for synergistic piezocatalytic and sono-activated chemotherapy (SACT)-augmented immunotherapy. Ultrasound (US) irradiation of the designed BPTL initiates a superior piezodynamic effect and produces ROS by piezocatalytic therapy to trigger ICD. Subsequently, the generated ROS breaks up the thioketal bonds in BPTL, thereby leading to the on-demand release of PTX for SACT and augmented ICD activation. In vivo evaluation demonstrated that BTPL with US irradiation significantly eradicated primary and distant metastatic tumors and markedly prevented the lung metastasis. This nanoplatform combines US-triggered piezocatalytic therapy and SACT for ICD stimulation, providing a robust strategy for amplifying piezocatalytic effect-mediated immune response against tumors.

Polyphenolic materials have been extensively explored for biomedical applications. However, most polymer-based polyphenols are synthesized by covalently grafting phenol groups on the backbone of polymers and more convenient synthetic strategy remains challenging. Herein, a general and robust strategy to synthesize polypeptide-based polyphenol via selective ortho-hydroxylation of poly(tyrosine) was developed to construct dynamic nanoparticles (GPCuD NPs) composed of Cu²⁺ and phenylboronic acid modified doxorubicin prodrug (DOX-PBA) via metal-phenol coordination interaction and pH-reversible phenylboronate ester bond, respectively. Furthermore, matrix metalloproteinase-2 (MMP-2)-cleavable GPLGLAG peptide was also included between the polyethylene glycol and polyphenol segments, endowing GPCuD NPs with tumor-specific accumulation and deep penetration through enzyme-triggered depegylation. Notably, Cu²⁺-chelated nanoparticles efficiently ameliorated the immunosuppressive tumor microenvironment via recruiting antitumor immune cells and repolarizing M2-type tumor-associated macrophages to M1 phenotype. The combination of cuproptosis-driven metalloimmunotherapy with DOX chemotherapy remarkably suppressed 4T1 orthotopic breast tumor growth by 81.9 % and established a long-term immune memory (effective memory T cells up to 30.8 %) to prevent lung metastasis. This study has demonstrated a generalizable polyphenol nanoplatform for tumor-targeted and cuproptosis-regulated combination cancer metalloimmunotherapy.

Tumor cells are major consumers of glutamine and glucose in the tumor microenvironment (TME), causing nutrient deficiency of immune cells, leading to immune escape and resistance to immunotherapy. However, pharmacological modulation would cause metabolic inhibition in both immune cells and tumor cells. Herein, a multifunctional nutrient transfer nanoCRISPR scaffold (FUEL) is fabricated to realize “nutrient transfer” from tumor cells to immune cells and remodel the metabolism in the TME, thus fueling cancer immunotherapy. FUEL is endowed with characteristics of enhanced blood circulation, specific tumor cell targeting, effective lysosomal escape, cascaded reactive-oxygen-species (ROS)-responsiveness, and ASCT2/GLUT1 dual gene knockout. Consequently, FUEL can restrict nutrient uptake of tumor cells thoroughly, increase glucose and glutamine in the TME remarkably to satisfy metabolic demands of immune cells, and reduce immunosuppressive metabolites concurrently. Metabolomics data shows that energy metabolism and biosynthesis are reduced in tumor cells but enhanced in immune cells. FUEL remarkably impedes the growth, metastasis, and recurrence of solid tumors in mice, further shows stronger anti-tumor immune responses and enhanced tumor inhibition in combination with anti-PD-L1 antibody. Overall, this nutrient transfer strategy enables a “one arrow aiming at three eagles” effect that induces a cascade amplification of antitumor immune responses for the maximized tumor therapy efficacy.

Immunotherapy occupies an increasingly important place in the field of tumor treatment. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which is responsible for sensing and responding to cytosolic DNA, stands out as a key player of the host innate immunity and a significant contributor to anti-tumor immunotherapy. Besides, it serves as the principal signaling pathway for type I interferon (IFN) production, coordinating the maturation and activation of various immune cells like dendritic cells (DCs) and CD8⁺ T cells, thus bridging innate and adaptive immunity. The increasing focus on essential metal nanoparticles, notably Mn²⁺, Zn²⁺ and Ca²⁺, and their roles in the induction of oxidative stress are of increasing interest in the application of tumor immunotherapy especially for the stimulation of cGAS-STING pathway. Recent advancements in metal-based nanomaterials present a promising avenue for anti-tumor immunotherapy based on cGAS-STING pathway activation. This review offers a comprehensive overview of how metal-based nanomaterials affect the cGAS-STING pathway, as well as discusses the latest findings on metal-based nanomaterials, providing insights into their potential uses in cancer immunotherapy grounded in the activation of the cGAS-STING pathway.

Radiotherapy is a crucial antineoplastic approach in clinical practice, but it often suffers from low therapeutic efficacy due to inadequate deposition of X-ray radiation and limited inhibition of metastatic tumors. Here, a bioinspired Hf-based metal-organic framework (Hf-MOF) nano-radiosensitizer (SHMR) is elaborately designed for boosting radio-immunotherapy by synergizing radio-sensitization with nitric oxide-assisted immune microenvironment remodeling. The engineered SHMR is constructed by wrapping RGD peptide-modified erythrocyte membrane onto sodium nitroprusside-loaded Hf-MOF. In vitro and in vivo experiments demonstrate that SHMR can induce immunogenic cell death and release abundant tumor-associated antigens to promote dendritic cells maturation and T cells activation under X-ray irradiation. Importantly, nitric oxide (NO) released from SHMR can not only relieve tumor hypoxia to alleviate radiotherapy resistance, but also reprogram tumor microenvironment, thereby reshaping the extracellular matrix barrier and enhancing immune cells infiltration. Specifically, SHMR in conjunction with αPD-L1 therapy exhibits favorable therapeutic outcomes in bilateral tumor and metastatic tumor models. This work creates a practical nano-radiosensitizer to achieve effective radiotherapy and NO-mediated tumor microenvironment reconstruction, providing a promising strategy for potentiating the radio-immunotherapy against “immune-cold” tumors.