Journal of Nanobiotechnology最新文献

Peritoneal carcinomatosis is an advanced stage of cancer with very limited treatment options. Locoregional immunotherapy is being evaluated as a way to improve efficacy and limit toxicity. This study assessed the efficacy of a cationic polymer/lipid-based transfection compound in delivering mRNA molecules intraperitoneally. Our investigation of the transfer of luciferase mRNA in murine models of peritoneal carcinomatosis revealed preferential luciferase expression in the omentum upon the intraperitoneal administration of complexed mRNAs. Macrophages were identified as key cells that capture and express the mRNA complexes, and accordingly, depletion of resident macrophages led to reduced reporter luciferase expression. To explore the therapeutic potential of this approach, mRNA complexes encoding single-chain interleukin-12 (IL12), an immunostimulatory molecule (mRNA-IL12), were investigated. mRNA-IL12-treated mice exhibited a significant survival advantage in models of peritoneal carcinomatosis and acquired immune memory, as shown upon subcutaneous rechallenge. Tumor microenvironment analyses revealed increased numbers of CD4⁺ and CD8⁺ T cells with a more proliferative phenotype, accompanied by decreased myeloid populations in the omentum. Overall, our study underscores the potential of mRNA complexes for efficient mRNA delivery, eliciting effective antitumor responses and modulating the tumor microenvironment to treat peritoneal carcinomatosis.

Diabetic wound therapy faces significant challenges due to the complexity of the wound microenvironment, especially dysregulated immune cell responses and persistent pro-inflammatory sate. Targeting immune cells to reverse pathological wound conditions has increasingly become a promising strategy to promote diabetic wound healing. It has been reported that prolonged memory to acute inflammation sensitizes epidermal stem cells (EpSCs) to tissue damage. The increasing importance of interactions between immune cells and tissue stem cells has raised interest in the potential of EpSCs to induce inflammatory adaptations in diabetic wounds, and meanwhile, the inflammation memory patterns also provide new insight in EpSCs for tissue repair. Here, bioinspired cell-derived mimetic nanovesicles (MNVs) were obtained from inflammation memory-activated EpSCs. LPS treatment could trigger acute inflammation response and activate inflammation memory. MNVs derived from LPS-pretreated EpSCs (LEM) can effectively promote diabetic wound healing by manipulating crucial neutrophil regulatory mechanisms. The in vitro and in vivo studies demonstrated that LEM could stimulate neutrophil mitochondrial metabolic reprogramming, overcome phenotypic switching deficiency of neutrophils, and skew neutrophils toward N2 anti-inflammatory phenotype via regulating miR-193a-5p/TLR4/ JNK/P38 MAPK pathways in diabetic models. Our findings highlighted the great potential of inflammation memory in EpSCs, and also provided an alternative for diabetic wound treatment.

Background: Uranium-induced kidney damage represents a major health concern due to its toxic effects, including mitochondrial dysfunction and inflammation. Mitochondrial DNA (mtDNA)-mediated pyroptosis is a critical pathway in the pathogenesis of renal injury. The toll-like receptor 4 / nuclear factor-kappa B (TLR4/NF-κB) signaling pathway plays a pivotal role in this process. Recent studies have shown that extracellular vesicles derived from adipose-derived stem cells (ADSCs-EVs) possess therapeutic potential due to their anti-inflammatory and regenerative properties. Incorporating ADSCs-EVs into arginine-glycine-aspartate (RGD), hydrogels may enhance their stability and therapeutic efficacy in vivo. This study aims explore the molecular mechanism by which RGD hydrogel-loaded ADSCs-EVs modulate mtDNA-mediated pyroptosis by suppressing the TLR4/NF-κB signaling pathway to alleviate uranium-induced kidney injury.

Results: Repairing mitochondrial dysfunction was found to mitigate mtDNA leakage, thereby inhibiting renal pyroptosis. ADSCs-EVs alleviated uranium-induced renal cell damage by suppressing the TLR4/NF-κB signaling pathway. In vivo animal experiments confirmed that RGD hydrogel-loaded ADSCs-EVs enhanced their stability in the body and improved their therapeutic efficacy against kidney injury.

Conclusion: Our findings reveal that RGD hydrogel-loaded ADSCs-EVs effectively inhibit the TLR4/NF-κB signaling pathway, preventing mtDNA-mediated pyroptosis and alleviating uranium-induced kidney damage. This elucidation provides a novel strategy for utilizing RGD hydrogel-loaded ADSCs-EVs in treating kidney injury.

Ferroptosis plays a critical role in myocardial ischemia-reperfusion injury (MIRI), posing a significant clinical challenge. Nanoenzymes like cerium oxide (CeO₂) hold promise for mitigating oxidative damage and inhibiting ferroptosis, but their delivery efficiency and biological activity require optimization. This study aims to develop a targeted nanozyme delivery system for MIRI treatment by integrating CeO₂ with mesoporous polydopamine (mPDA) and dexrazoxane (DXZ) to achieve synergistic therapeutic effects. A biomineralization technique was used to synthesize CeO₂ nanoparticles (2-3 nm) within mPDA, forming ~ 130 nm composite nanoparticles (Ce@mPDA). Surface modifications with cardiac homing peptide (CHP) and triphenylphosphine (TPP) enabled hierarchical targeting to injured myocardium and mitochondria. DXZ-loaded Ce@mPDA-C/P nanoparticles (D/Ce@mPDA-C/P) were evaluated in vitro and in a MIRI mouse model for their effects on oxidative stress, ferroptosis, apoptosis, inflammation, and cardiac function. D/Ce@mPDA-C/P nanoparticles exhibited robust ROS scavenging, sustained DXZ release, and efficient myocardial and mitochondrial targeting. The D/Ce@mPDA-C/P system significantly reduced oxidative stress, upregulated GPX4 expression, inhibited ferroptosis, and modulated the inflammatory microenvironment. Long-term studies in a MIRI mouse model demonstrated reductions in myocardial fibrosis and improvements in cardiac function, including enhanced fractional shortening and ejection fraction. This hierarchical targeting delivery system effectively combines the antioxidant properties of CeO₂ with the iron-chelating effects of DXZ, providing a promising therapeutic strategy for MIRI. This approach may expand the clinical use of DXZ and advance nanomedicine-based interventions for myocardial repair.

The continuously evolving Omicron subvariants has diminished the effectiveness of almost all RBD-targeted antibodies in neutralizing these subvariants. The development of broad-spectrum neutralizing antibodies is desired for addressing both current and future variants. Here, we identified a shark-derived nanobody, 79C11, that can neutralize all Omicron subvariants tested so far, including BA.1 to JN.1 and KP.2, and exhibits comparable neutralizing potency against SARS-CoV-1 and pangolin coronavirus. Intranasal instillation of 79C11 can effectively prevent the infection of Omicron subvariant XBB in vivo. The designs of multivalent forms of 79C11 further enhance binding and neutralizing activity. Epitope mapping and structure simulation reveal that this nanobody binds to a highly conserved HR1 region in S2 domain of the spikes from all sarbecoviruses, suggesting that a universal vaccine may be designed to target this region for eliciting broadly neutralizing antibody response. This nanobody can also be developed as an intranasally administered prophylactic agent for preventing the infection of current and likely future SARS-CoV-2 variants, as well as other animal derived sarbecoviruses that may infect humans.

The bacterial synthesis of fluorescent semiconductor nanoparticles or quantum dots (QDs), presents a sustainable method for producing nanomaterials with customized optical properties and significant technological potential. However, the underlying cellular mechanisms for this process remain elusive. Specifically, the role of cellular structures in QD generation has not been thoroughly investigated. In this study, we examined the morphological changes in Escherichia coli during the biosynthesis of cadmium sulfide (CdS) QDs, using a strain overexpressing the gshA gene to promote QD biosynthesis through increased glutathione (GSH) levels. Microscopy analyses revealed that fluorescence emission associated with QDs was concentrated at the cell poles, along with fluorescence emission from small spherical cells, a phenomenon exclusively detectable during QD biosynthesis. Transmission electron microscopy (TEM) revealed electron-dense nanomaterials localized at the cell poles. Furthermore, it was demonstrated the formation of minicell-like structures (∼ 0.5 μm in diameter) originating from these poles under biosynthesis conditions. These minicells encapsulated nanometric electron-dense material. Additional analyses indicated that minicells contained inclusion bodies, likely formed due to gshA overexpression and cadmium stress. Our findings confirms the role of minicells as a bacterial mechanism for sequestering cadmium at the cell poles and expelling the metal in the form of nanoparticles. This underscores the importance of minicells in bacterial physiology and stress responses, introducing a novel mechanism for heavy metal detoxification in bacteria.

The ever-increasing chemoresistance of osteosarcoma (OS) has been observed in the recent decades, impeding OS therapeutic improvement and posing an urgency to exploit to the alternative and/or supplementary therapies for the optimization of OS chemotherapeutic regimen. Ferroptosis, a regulated cell death, has been identified as a natural anticancer mechanism as well as a synergist for chemotherapeutics in various cancers. Herein, we affirmed the tumor-suppressing properties of eriodictyol and illustrated that its antitumor effects might ascribe to the ferroptosis-inducing activity, in which eriodictyol could bind with BACH1 to repress the transcription and translation of GPX4 and eventually result in the GPX4-related ferroptosis. Further investigation found that eriodictyol could exhibit a synergistic effect with cisplatin, facilitating the antitumor effects of cisplatin. Lastly, through utilizing hollow mesoporous prussian blue nanocubes loaded with eriodictyol and cisplatin, we formed the ferroptosis-synergistic nanocomplexes to facilitate OS cells ferroptosis and cisplatin sensitivity. Through direct catalytic oxidation of unsaturated lipids, exogenous iron delivery, GSH exhaustion, and GPX4 transcriptional inhibition, this ferroptosis-synergistic nanocomplex could excellently enhance OS cells ferroptosis in both vitro and vivo, with no obvious organ injury observed. Therefore, our ferroptosis-synergistic nanocomplex may represent a promising alternative therapeutic strategy for OS patients.

There are abundant natural products resources and extensive clinical use experience in China. However, the active components of natural products generally have problems such as poor water solubility and low bioavailability, which limit their druggability. Carrier-free nanoparticles, such as nanocrystals, self-assembled nanoparticles, and extracellular vesicles derived from both animal and plant sources, have great application potential in improving the safety and efficacy of drugs due to their simple and flexible preparation methods, high drug loading capacity and delivery efficiency, as well as long half-life in blood circulation. It has been widely used in biomedical fields such as anti-tumor, anti-bacterial, anti-inflammatory and anti-oxidation. Therefore, based on the natural products that have been used in clinic, this review focuses on the advantages of carrier-free nanoparticles in delivering active compounds, in order to improve the delivery process of natural products in vivo and improve their draggability.

Uncontrolled acute and persistent bleeding, as well as with infection, is a great challenge because of the high mortality during treating the patients with injuries, complex surgery or bone marrow failure. Here, we develop an external form of natural components which is based on phosphorylated methacrylated gelatin (GelMA, G) cryogel (GP) loaded with tannic acid (TA)-mixed copper ion (Cu²⁺) mesoporous bioactive glasses (MBG), named after GP@MBG-Cu-TA cryogel, to address the goals of reduce persistent bleeding and enhance antibacterial activity. Structurally, GP@MBG-Cu-TA cryogel is based on GP, MBG loaded with TA and Cu²⁺ adheres to GP via hydrogen bonding. In vitro, GP@MBG-Cu-TA cryogel displays a good biocompatibility, hemostatic and antimicrobial capability. In vivo studies, GP@MBG-Cu-TA cryogel can enhance the hemostatic effect in the liver injury in SD rats for the acute bleeding, as well as in the aplastic anemia and hemophilia A mice with tail amputation for the persistent bleeding. In addition, GP@MBG-Cu-TA cryogel accelerates the skin wound repair in the mice with the bacterial contamination at the injury site. In sum, GP@MBG-Cu-TA cryogel is not only endowed with dual function of hemostatic and antimicrobial capability, but also can stop bleeding of the objects with either normal or abnormal coagulation function. Thus, GP@MBG-Cu-TA cryogel provides a promising candidate dressing for managing bleeding and bacterial complications in clinic.

Peripheral arterial disease (PAD) poses a global health challenge, particularly in its advanced stages known as critical limb ischemia (CLI). Conventional treatments often fail to achieve satisfactory outcomes. Patients with CLI face high rates of morbidity and mortality, underscoring the urgent need for innovative therapeutic strategies. Recent advancements in biomaterials and biotechnology have positioned biomaterial-based vascularization strategies as promising approaches to improve blood perfusion and ameliorate ischemic conditions in affected tissues. These materials have shown potential to enhance therapeutic outcomes while mitigating toxicity concerns. This work summarizes the current status of PAD and highlights emerging biomaterial-based strategies for its treatment, focusing on functional genes, cells, proteins, and metal ions, as well as their delivery and controlled release systems. Additionally, the limitations associated with these approaches are discussed. This review provides a framework for designing therapeutic biomaterials and offers insights into their potential for clinical translation, contributing to the advancement of PAD treatments.