Nano Today最新文献

The regional deposition of inhaled particulate matter (PM) in the respiratory tract determines its biological fate and lung toxicity. While it is widely accepted that the size of PM plays a predominant role in affecting lung deposition, the impact of other physicochemical properties, especially hydrophobicity, remains unclear. This knowledge gap exists, in part, due to the absence of standard methods to characterize the hydrophobicity of PM. Here, we developed a novel nonionic dye partitioning method to quantitatively characterize the hydrophobicity of PM. The use of a nonionic dye, rhodamine B, effectively eliminates experimental artifacts arising from unwanted dye adsorption due to electrostatic interactions, thus significantly improving the accuracy and applicability of the method. Through an intranasal mouse exposure model, we discovered that the lung deposition of four types of PM originated from common anthropogenic sources, including PM2.5, dust, biochar, and carbon black, is mediated by their hydrophobicity. The most hydrophobic PM tends to be trapped in the nasal cavity, whereas the least hydrophobic PM penetrates deep into the alveoli, inducing severe lung inflammation. The hydrophobicity-dependent deposition of PM in the respiratory tract offers novel insights into understanding the acute lung toxicity of inhaled PM and provides a foundation for the design of safer and more efficacious inhalable medicines. Furthermore, the nonionic dye partitioning method shows promise as a user-friendly and cost-effective approach for characterizing the hydrophobicity of PM.

Oncolytic adenoviruses (OA) are promising therapeutics for glioblastoma (GBM) due to their unique capability of selectively lysing tumor cells and activating the immune response. However, their therapeutic potential is often impeded by limited cellular internalization caused by low expression of OA receptors, as well as restricted OA proliferation due to antiviral responses. In this work, a novel type of OA, named nanosynergist-engineered OA (nsOA), was developed by functionalizing the viral surface with siRNA-loaded hyperbranched polymers. The nanosynergist not only enhanced the infectivity of OA but also augmented virus replication, ultimately potentiating their oncolysis efficacy. We revealed that the enhanced replication of the virus was initiated by the downregulation of signal transducer and activator of transcription-3, which suppressed the transcription of interferon-stimulated genes, ultimately circumventing the antiviral defense of tumor cells. Furthermore, the innate ability of OA to disrupt endosomal membranes was found to improve the endosomal escape of the nanosynergist, creating synergistic effect that amplified the therapeutic benefits. A single dose of nsOA markedly increased the production of progeny viruses and prolonged the survival of mice. Collectively, these results provide an effective and valuable strategy to engineer OA, which may lead to innovative immunotherapies for various cancers.

Heterogeneous catalysts play a pivotal role in the chemical industry. Pretreatments in reducing or oxidizing atmospheres have been widely utilized to alter the structure of heterogeneous catalysts, with the aim of enhancing their catalytic performance. However, the pretreatment atmosphere can, at times, trigger unexpected structural changes in catalysts and even lead to catalytic degradation. Hence, the selection of an appropriate pretreatment atmosphere for heterogeneous catalysts is critical and requires a clear understanding of their corresponding dynamic evolution to improve their performance in a targeted manner, particularly relying on in situ observation. In this study, a promising CO oxidation catalyst, LaFeO₃ supported Au nanoparticles (Au/LFO) is selected, and the influence of the pretreatments in different atmospheres on Au/LFO is explored by using in situ transmission electron microscopy (TEM) and density functional theory (DFT) calculation. Our findings reveal that the commonly used reducing pretreatment for noble-metal catalysts triggered strong metal-support interactions in Au/LFO, suppressing its CO adsorption performance. In contrast, the oxidizing pretreatment preserves the metallic Au and the metal/support interface as efficient active sites to promote CO oxidation activity and stability simultaneously. This work discloses the structure evolution at the interface between noble metals and perovskite oxide supports in response to different gas phase treatments and clarifies their structure-property relationships.

Increasing concerns surround nanoplastic’s health risks owing to global exposure emphasize clear understanding of their dynamic distribution and organ-specific molecular effects. We assessed the health risks associated with nanoplastics (100 nm) following oral ingestion. Using a fluorescent tracking system, we demonstrated their recyclability through gastrointestinal tract-liver-gallbladder axis, with specific accumulation in the gallbladder. Pathological alterations in the gallbladder and single-cell RNA sequencing data indicated that short-term (three weeks) exposure induces gallbladder epithelial hyperplasia, whereas long-term exposure (six weeks) induces progressive hyperplasia, epithelial-mesenchymal transition (EMT), and fibrosis. Nanoplastic exposure facilitates neutrophil extracellular trap (NET) formation. Various nanoplastics were identified in human gallbladder bile samples using scanning electron microscopy (SEM) and Raman spectroscopy. Consistently, epithelial hyperplasia and neutrophil infiltration were observed in the gallbladder tissues, alongside nanoplastic detection in the bile. Our findings offer insights into the understanding of the enterohepatic-biliary recycling route of nanoplastics and their potential toxic consequences.

The intricate microenvironment often hinders diabetic wounds from following a normal healing process, marked by prolonged low-grade inflammation, thereby slowing or stalling wound healing. Nanomedicine stands as a pivotal branch in the evolution of therapeutic strategies, yet grapples with inherent conflicting traits – the ROS-dependent antibacterial properties of most materials and the anti-inflammatory ROS-scavenging capabilities. This study introduces a multifunctional MOF-199/GO nanocomposite designed to promote diabetic wound healing by its robust ROS scavenging capacity, ROS-independent antibacterial and anti-biofilm properties, and the ability to modulate wound microenvironments. In a skin wound model on type I diabetes rats, the addition of MOF-199/GO efficiently orchestrates the healing process into the defined phases of inflammation, proliferation, and remodeling, achieving a remarkable 96 % wound closure by day 10. When employed as a drug, MOF-199/GO exhibits minimal biological toxicity in vivo. Moreover, when combined with various dressing materials, the drug’s performance remains unchanged, indicating its practical application value.

Cancer stem-like cells (CSCs) have a well-established role in mediating tumor relapse and resistance towards chemotherapy and radiation therapy. Photothermal therapy (PTT) is an efficient therapeutic strategy that uses light and photothermal agents to generate hyperthermia in tumors and kill cancer cells. However, due to the heterogeneity and drug resistance of CSCs, some of them may survive from PTT and cause recurrence and metastasis of tumors. In the study, we present a sequential dual-wavelength light-controlled drug delivery strategy, which combines 656 nm light-triggered drug release to inhibit cancer stemness, followed by 808 nm light-activated PTT to eradicate bulk tumors. The first light irradiation induces the release of γ-secretase inhibitor MK-0752 to deactivate Notch pathway, which is a key regulator of CSCs. Subsequently, the second light irradiation triggers hyperthermia to effectively kill tumor cells. Our findings demonstrate that inhibiting cancer stemness increases tumor sensitivity to PTT, resulting in effective growth inhibition of primary tumors with repressed tumorgenicity. This innovative dual-wavelength strategy holds promise for enhancing the efficacy of PTT in addressing the challenges posed by CSCs-rooted heterogeneity and drug resistance.

Implant-associated infection (IAI) has significantly impeded the progress of surgery, and a properly functioning antibacterial immune response is critical for preventing persistent infection and reinfection. However, the efficacy of current infection immunotherapy remains considerably suboptimal, primarily because of the lack of validated therapeutic targets and interventions. Herein, we identify a bismuth-based metal organic frameworks (Bi-MOF) as an efficient intracellular hydrogen sulfide (H₂S) scavenger that promotes the antibacterial response of macrophages through the inhibition of hypoxia inducible factor-1α (HIF-1α) S-sulfhydration and subsequent ubiquitin-dependent degradation. The reduction in H₂S levels by Bi-MOF in vivo contributes to accelerated the clearance of bacteria, prevention of bone destruction, and augmentation of innate immunity in a mouse IAI model. Moreover, Bi-MOF also boost bacteria-specific adaptive immunity, thereby generating long-lasting protection against reinfection. Together, our results demonstrate that H₂S-responsive Bi-MOF offer a promising immunotherapeutic approach as a potential alternative to antibiotics for managing stubborn IAIs.

Antibody-drug conjugate (ADC)-based tumor-targeting therapies have demonstrated clinical success in selective drug delivery for cancer treatment. However, the effectiveness of these strategies is hindered by the low amount of loaded payload, lack of sustained efficacy, and insufficient therapeutic performance. In this study, we introduce a novel in situ aggregation-based targeting system using two combinable nanoparticles (NP) that leverage the biocompatible and specific interaction between complementary protamine and heparin molecules. To demonstrate it, we developed protamine-based nanoparticles (PPNC NP) containing cytotoxic negatively charged curcumin (NCur), and heparin-based nanoparticles (HDFe NP) encapsulating doxorubicin and Fe³⁺. The NP-NP treatment successfully formed aggregates at targeted tumor sites. Our findings demonstrate that the initial administration of PPNC NP effectively targets the tumor and the subsequent administration of complementary HDFe NPs results in their significant accumulation in the tumor tissue, directed by the ‘guidance effect’ of PPNC NPs. This sequence of events promotes the formation of in situ aggregates within the tumor tissue, leading to prolonged nanoparticle accumulation, ferroptosis and immunogenic cell death (ICD). In conclusion, our study demonstrates the effectiveness of a biocompatible and in situ aggregating nanoparticle-nanoparticle system as a solution for overcoming the limitations of current nanoparticle-based delivery systems.

In situ vaccinations that specifically generate tumor antigens and drive the cancer-immunity cycle to kill tumor cells have emerged as a promising therapeutic strategy for cancer treatment. However, insufficiency in a series of processes involving tumor antigens, such as tumor antigen release and lymphatic transportation, hinders antitumor immunity. Here, we prepared a series of lipid-polymer hybrid nanoformulations, and optimized a cationic lipid-polymer nanoparticles (DOTAP-hNPs), comprising a hybrid of poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), for efficient in situ vaccination against cancer. DOTAP-hNPs efficiently induced immunogenic cell death (ICD) of tumor cells via inhibiting the ATPase activity and consequently generate an abundance of tumor antigens in situ. And then, the DOTAP-hNPs can capture these antigens and drive their lymphatic navigation into antigen-presenting cells (APCs) in draining lymph nodes (dLNs). Thus, intratumoral administration of DOTAP-hNPs significantly promoted APC activation in dLNs and T-cell intratumoral infiltration, eliciting robust systemic antitumor immune responses and synergistically enhancing the efficacy of checkpoint blockade therapy in several tumor models (CT26, B16F10 and 4T1). Our research presents an accessible strategy to prime systemic immunity and improve personalized cancer immunotherapy.