Nano Today最新文献

Chronic neuromicrovascular dysfunction and its induced multifaceted neuropathology involving the interaction of cellular differential pathogenic mechanisms pose challenges to the precise treatment of Alzheimer’s disease (AD). Here we report the development of an ellagic acid-derived self-assembled micellar SIRT1 activator (REn) that enables cross-scale targeted remodeling of neurovascular and neurometabolic coupling in AD. Efficient transcytosis of the receptor for advanced glycation endproducts by modified peptides allows for programmed delivery of REn to cerebral microvessels and parenchymal neurons. The resulting SIRT1 cascade activation enhances endothelial nitric oxide signaling-mediated cerebral blood flow and the blood-brain barrier integrity, while promoting neuronal mitochondrial biogenesis and glucose metabolic patterns toward oxidative phosphorylation. This multipronged remodeling strategy achieves a cooperative normalization of brain energy supply and β-amyloid clearance in AD mice, showing profound improvement in cognitive impairment. This work provides an advanced pharmacological option for cross-scale targeted treatment of neurodegenerative diseases associated with neurovascular dysfunction.

Emerging evidence has revealed that induction of pyroptosis is a promising strategy for cancer therapy. However, it remains challenging to specifically evoke pyroptotic cancer cell death paradigm while sparing other programmed cell death pathways. Here, we report a general nanostrategy towards elicitation of precise oxidative stress in early endosomes (EE) by several nanosized photosensitizers (NPS) for robust pyroptotic cancer therapy. The spatiotemporally subcellular trafficking of NPS can regularly tune the pyroptosis-inducing activity of endocytic organelle stress. NPS-enabled EE oxidative stress (NPS_ee) initiates universal and robust gasdermin-E-mediated pyroptosis across different nanocarriers and cancer cell lines with up to 21.4-fold higher sensitivity, as compared with the traditional lysosomal stress. This EE-stressed nanostrategy achieves complete eradication of primary tumors with efficient immune response and long-lasting cancer prevention. This study provides guidelines for design of nanomedicines with pyroptosis-inducing activity for cancer therapy.

The study of conventional lateral memristors has been in a slow stage of development due to the dependence of the atomic defect migration or local phase transition in two-dimensional (2D) materials. Here, a novel transversal memristor based on the flexoelectric effect induced by a bent atomic laminated structure is proposed. The memristor exhibits desirable resistive switching performance, including a current ON/OFF ratio of approximately 10⁵, forming-free operation, high yield of 97 %, and low cycle-to-cycle variation of only 7.4 %. The stable analog memristive behavior could be attributed to the dynamic modulation of the barrier between suspended and flat regions by external voltage biases. Further, the volatile resistance switching characteristics have successfully emulated key features of multi-field perceptual artificial nociceptors, including threshold, “no adaptation” etc. This work demonstrates a new resistive switching phenomenon in transversal 2D material devices, and opens a new way for the development of intelligent adaptive artificial sensory systems.

Bone metastasis of lung cancer often leads to severe clinical complications and high mortality rates. The current treatment methods mostly demonstrate limited efficacy due to their inadequate bone targeting capability and insufficient impact on the underlying mechanism of bone metastasis. From the bone metastasis in lung cancer patients, we find that integrin β1 (ITGB1) is a pivotal factor in the pathogenesis of lung cancer bone metastasis, influencing the proliferation, apoptosis, migration, and invasion of lung cancer cells. Therefore, we develop an ITGB1 short-interfering RNA (siRNA)-loaded cationic liposome to treat lung cancer bone metastasis and co-delivered zoledronic acid to enhance its bone-targeting efficacy (Z&S@CLs). The Z&S@CLs exhibit good capability in targeting bones, effectively suppressing the growth of existing bone metastasis tumors and delaying the occurrence of bone metastasis in vivo. Mechanistically, Z&S@CLs prevent the extravascular invasion of tumor cells by modulating the cellular cytoskeleton, inhibiting focal adhesion formation, and suppressing the PI3K/Akt signaling pathway. In summary, these findings provide a promising strategy based on ITGB1 for treating lung cancer bone metastasis.

Oral squamous cell carcinoma (OSCC), a prevalent malignancy with high recurrence and metastasis rates, poses significant treatment challenges, particularly the prevention of lymph node metastasis. The development of a powerful photothermal agent for combined photothermal immunotherapy that inhibits OSCC metastasis remains challenging. Our study introduces an approach utilizing nanoparticles synthesized from a novel polymer with strong electron donor-acceptor structures for Near-Infrared II (NIR-II) photothermal therapy (PTT) by increasing intermolecular π-π interactions and enhancing non-radiative transitions. Owing to the superior tissue penetration capabilities of NIR-II region, these nanoparticles exhibit exceptional photothermal conversion, stability, and biocompatibility, making them ideal for deep-seated tumor ablation with minimal off-target effects. Mechanistically, the RNA-sequencing analysis revealed the upregulation of crucial apoptosis-related and antigen-presenting pathways in PTT-treated cancer cells. Polymer nanoparticles can intensify the immunogenic cell death to elicit a tumor-related immune response, releasing dramatically tumor-associated antigens, and activating damage-associated molecular patterns to eliminate tumor cells synergistically. As evidenced by our comprehensive in vivo OSCC mouse model, subsequent detailed approaches further demonstrated significant cancer cell eradication and induction of a strong immunogenic response to inhibit lymph node metastasis. Our study highlights the potential of tumor cell ablation and immunogenic activation dual therapy for targeting both primary and metastatic OSCC, suggesting a new direction for reshaping current therapeutic strategies for OSCC treatment.

Radiation therapy is crucial in combating malignant tumors, yet its damage to the microvascular system can significantly impair patient recovery and prognosis. Although current radiation protection measures mitigate free radical damage to target organs, they fall short in safeguarding the surrounding microvasculature. This study pioneers the use of the matrigel plug angiogenesis model to investigate the application of the water-soluble fullerene derivative Fullerenol in microvascular radioprotection, aiming to effectively protect and repair the microvascular system during radiation therapy, thereby reducing its adverse effects on healthy tissues. Our findings demonstrate that Fullerenol not only efficiently scavenges free radicals, reducing radiation-induced damage, but also promotes endothelial cell proliferation, facilitating the repair of damaged microvasculature and surrounding tissues. Additionally, Fullerenol was found to inhibit Caspase-3 and activate the PI3K/AKT (Phosphoinositide 3-kinase/Protein kinase B) proliferation metabolic pathway and its downstream proteins, such as eNOS and VEGF (Endothelial nitric oxide synthase/Vascular endothelial growth factor), decreasing endothelial cell apoptosis and maintaining vascular proliferation and angiogenesis potential. This research provides a new option for microvascular radioprotection and offers fresh insights into the repair of tissues damaged by radiation therapy.

The musculoskeletal system involves various cell types that participate in maintaining bone homeostasis, which is crucial for balancing osteogenesis and osteoclastogenesis. Imbalances in bone homeostasis can lead to numerous musculoskeletal disorders, including osteoarthritis (OA) and osteoporosis (OP). In recent years, there has been growing interest in osteoimmunity due to its significant regulatory impact on bone homeostasis. Various cell types, including macrophages, T cells, and B cells, participate in osteoimmunology and regulate bone homeostasis. Currently, extracellular vesicles (EVs) play crucial roles in cell-to-cell communication. In particular, mesenchymal stem cell (MSC)-derived EVs have been reported as potential immunoregulators in certain immune-related diseases. This comprehensive review aims to present recent advancements in the understanding of the immunoregulatory effects of MSC-derived EVs in musculoskeletal diseases. In addition, we discuss the immunoregulatory effects of MSC-EVs on programed cell death in osteoblasts, osteoclasts, and chondrocytes, and the effect of this modulation on bone homeostasis. Moreover, we provide insights into the potential applications of MSC-EVs in the management of prevalent musculoskeletal disorders, including OP, OA, and bone fractures. In conclusion, this review emphasizes current advancements in research and future directions in MSC-EV-based therapies for musculoskeletal disorders.

Inflammatory reactions are closely relevant to infectious ailments, autoimmune maladies, cardiovascular afflictions and neurological disorders. As a pivotal organelle crucial for the maintenance of cellular homeostasis, mitochondria influence inflammation significantly. However, owing to mitochondria's unique architecture and characteristics, achieving effective regulation of mitochondria is a challenge. Fortunately, with the progress in nanomaterials within recent years, scientists have achieved effective mitochondrial regulation to ameliorate inflammation. Therefore, we provide a timely overview for summarizing and prospecting this direction. First, we highlight how the imbalance of mitochondrial quality and mitochondrial function can aggravate inflammation. Second, we list different nanomaterials for targeting mitochondria. Third, we summarize various strategies for alleviating inflammation based on mitochondria-targeted nanomaterials. Finally, we explore the current challenges and future opportunities for mitochondria-targeted nanomaterials. This review aims to provide new possibilities for harnessing mitochondria-targeted nanomaterials towards inflammation-related disorders.

Infectious diseases, particularly those caused by multidrug-resistant pathogenic microorganisms, have posed a severe threat to human health and remain an ongoing public health concern worldwide. Recently, phototherapy stands out for its tremendous potential in treating infectious diseases, attributable to its impressive controllability, minimal invasiveness, and broad-spectrum antimicrobial capabilities. This review summarizes the operating principles of phototherapy and its application in combating infectious diseases caused by bacteria, viruses, and fungi. It provides a detailed explanation of the structure-performance relationships of photothermal agents and photosensitizers. Additionally, it discusses the current challenges, limitations, and potential future directions in phototherapy development, hoping to inspire future advancements and translational applications of phototherapy in infection control.

Melanoma is a tumor sensitive to immune response and its immunotherapy has been a research hotspot in recent years. By fusion of melanoma cell membranes and bacterial exosomes through sequential extrusion, we herein design a three-in-one multi-antigenic nanovaccine, namely TBM, to rapidly target immune system. TBM can induce RAW264.7 macrophage cells to differentiate into M1 type cells to release cytotoxic cytokines. It can also promote the maturation and antigen presentation of bone marrow-derived dendritic cells, thus activating spleen T cells to kill B16F10 melanoma cells in vitro. TBM can significantly inhibit the growth and metastasis of melanoma in vivo, and prolong the lifetime of mice, suggesting the preventive effects of vaccines. Further, we integrate cell membranes from mouse melanoma tissues into a novel personalized therapeutic vaccine, namely autologous TBM (ATBM). ATBM combined with Anti PD1 can activate anti-tumor immune response and increase the survival rate of melanoma allografted mice, as supported by eukaryotic reference mRNA-Seq transcriptome sequencing. Generally, this study demonstrates the preventive and therapeutic effects of biomimetic nanovaccines against melanoma, which may be extended to design personalized tumor vaccines for all tumors with immunogenicity, showing great clinical perspectives.