Journal of Nanobiotechnology最新文献

Background: Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. In vitro expansion is necessary to provide clinical-grade quantities of mesenchymal stem cells; however, it has been reported to cause replicative senescence and undefined dysfunction in mesenchymal stem cells. Quality control assessments of in vitro expansion have rarely been addressed in ongoing trials. Young small extracellular vesicles from the remnant pulp of human exfoliated deciduous teeth stem cells have demonstrated therapeutic potential for diverse diseases. However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines.

Results: We demonstrated that mitochondrial structural disruption precedes cellular dysfunction during bone marrow-derived mesenchymal stem cell replication, indicating mitochondrial parameters as quality assessment indicators of mesenchymal stem cells. Dynamin-related protein 1-mediated mitochondrial dynamism is an upstream regulator of replicative senescence-induced dysfunction in bone marrow-derived mesenchymal stem cells. We observed that the application of young small extracellular vesicles could rescue the pluripotency dissolution, immunoregulatory capacities, and therapeutic effects of replicative senescent bone marrow-derived mesenchymal stem cells. Mechanistically, young small extracellular vesicles could promote Dynamin-related protein 1 translocation from the cytoplasm to the mitochondria and remodel mitochondrial disruption during replication history.

Conclusions: Our findings show that Dynamin-related protein 1-mediated mitochondrial disruption is associated with the replication history of bone marrow-derived mesenchymal stem cells. Young small extracellular vesicles from human exfoliated deciduous teeth stem cells alleviate replicative senescence by promoting Dynamin-related protein 1 translocation onto the mitochondria, providing evidence for a potential rejuvenation strategy.

Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.

Adverse effects and multidrug resistance remain significant obstacles in conventional cancer therapy. Nanomedicines, with their intrinsic properties such as nano-sized dimensions and tunable surface characteristics, have the potential to mitigate the side effects of traditional cancer treatments. While nanomaterials have been widely applied in cancer treatment, challenges such as low targeting efficiency and poor tumor penetration persist. Recent research has shown that anaerobic bacteria exhibit high selectivity for primary tumors and metastatic cancers, offering good safety and superior tumor penetration capabilities. This suggests that combining nanomaterials with bacteria could complement their respective limitations, opening vast potential applications in cancer therapy. The use of bacteria in combination with nanomaterials for anticancer treatments, including chemotherapy, radiotherapy, and photothermal/photodynamic therapy, has contributed to the rapid development of the field of bacterial oncology treatments. This review explores the mechanisms of bacterial tumor targeting and summarizes strategies for synthesizing bacterial-nanomaterial and their application in cancer therapy. The combination of bacterial-nanomaterial hybrids with modern therapeutic approaches represents a promising avenue for future cancer treatment research, with the potential to improve treatment outcomes for cancer patients.

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.

The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe²⁺ (DOX-Fe²⁺), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe²⁺/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.

The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy.

Background: Manganese ions (Mn²⁺) combined with adjuvants capable of damaging and lysing tumor cells form an antitumor nano-modulator that enhances the immune efficacy of cancer therapy through the cascade activation of the cyclic GMP-AMP interferon gene synthase-stimulator (cGAS-STING) pathway, which underscores the importance of developing antitumor nano-modulators, which induce DNA damage and augment cGAS-STING activity, as a critical future research direction. METHODS AND RESULTS: We have successfully synthesized an antitumor nano-modulator, which exhibits good dispersibility and biosafety. This nano-modulator is engineered by loading manganese dioxide nanosheets (M-NS) with zebularine (Zeb), known for its immunogenicity-enhancing effects, and conducting targeted surface modification using hyaluronic acid (HA). After systemic circulation to the tumor site, Mn²⁺, Zeb, and reactive oxygen species (ROS) are catalytically released in the tumor microenvironment by H⁺ and H₂O_2. These components can directly or indirectly damage the DNA or mitochondria of tumor cells, thereby inducing programmed cell death. Furthermore, they promote the accumulation of double-stranded DNA (dsDNA) in the cytoplasm, enhancing the activation of the cGAS-STING signalling pathway and boosting the production of type I interferon and the secretion of pro-inflammatory cytokines. Additionally, Zeb@MH-NS enhances the maturation of dendritic cells, the infiltration of cytotoxic T lymphocytes, and the recruitment of natural killer cells at the tumor site.

Conclusions: This HA-modified manganese-based hybrid nano-regulator can enhance antitumor therapy by boosting innate immune activity and may provide new directions for immunotherapy and clinical translation in cancer.

Ischemic stroke is a common cause of mortality and severe disability in human and currently lacks effective treatment. Neuronal activation and neuroinflammation are the major two causes of neuronal damage. However, little is known about the connection of these two phenomena. This study uses middle cerebral artery occlusion mouse model and chemogenetic techniques to study the underlying mechanisms of neuronal excitotoxicity and severe neuroinflammation after ischemic stroke. Chemogenetic inhibition of neuronal activity in ipsilesional M1 alleviates infarct area and neuroinflammation, and improves motor recovery in ischemia mice. This study identifies that ischemic challenge triggers neuron to produce unique small extracellular vesicles (EVs) to aberrantly activate adjacent neurons which enlarge the neuron damage range. Importantly, these EVs also drive microglia activation to exacerbate neuroinflammation. Mechanistically, EVs from ischemia-evoked neuronal activity induce neuronal apoptosis and innate immune responses by transferring higher miR-100-5p to adjacent neuron and microglia. MiR-100-5p can bind to and activate TLR7 through U₁₈U₁₉G₂₀-motif, thereby activating NF-κB pathway. Furthermore, knock-down of miR-100-5p expression improves poststroke outcomes in mice. Taken together, this study suggests that the combination of inhibiting aberrant neuronal activity and the secretion of specific EVs-miRNAs may serve as novel methods for stroke treatment.

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC.

Magnetic nanoparticles offer many exciting possibilities in biomedicine, from cell imaging to cancer treatment. One of the currently researched nanoparticles are magnetosomes, magnetite nanoparticles of high chemical purity synthesized by magnetotactic bacteria. Despite their therapeutic potential, very little is known about their degradation in human cells, and even less so of their degradation within tumours. In an effort to explore the potential of magnetosomes for cancer treatment, we have explored their degradation process in a 3D human lung carcinoma model at the subcellular level and with nanometre scale resolution. We have used state of the art hard X-ray probes (nano-XANES and nano-XRF), which allow for identification of distinct iron phases in each region of the cell. Our results reveal the progression of magnetite oxidation to maghemite within magnetosomes, and the biosynthesis of magnetite and ferrihydrite by ferritin.