Journal of Nanobiotechnology最新文献

The abnormal structure of tumor vascular seriously hinders the delivery and deep penetration of drug in tumor therapy. Herein, an integrated and tumor microenvironment (TME)-responsive nanocarrier is designed, which can dilate vessle and improve the drug penetration by in situ releasing nitric oxide (NO). Briefly, S-nitroso-glutathione (GSNO) and curcumin (Cur) were encapsulatd into the Cu-doped zeolite imidazole framework-8 (Cu-ZIF-8) and modified with hyaluronic acid. The nanocarrier degradation in the weakly acidic of TME releases Cu²⁺, then deplete overexpressed intratumourally glutathione and transformed into Cu⁺, thus disrupting the balance between nicotinamide adenine dinucleotide phosphate and flavin adenine dinucleotide (NADPH/FAD) during the metabolism homeostasis of tumor. The Cu⁺ can generate highly toxic hydroxyl radical through the Fenton-like reaction, enhancing the chemodynamic therapeutic effect. In addition, Cu⁺ also decomposes GSNO to release NO by ionic reduction, leading to vasodilation and increased vascular permeability, significantly promoting the deep penetration of Cur in tumor. Afterwards, the orderly operation of cell cycle is disrupted and arrested in the S-phase to induce tumor cell apoptosis. Deep-hypothermia potentiated 2D/3D fluorescence imaging demonstrated nanocarrier regulated endogenous metabolism homeostasis of tumor. The cascade-catalysed multifunctional nanocarrier provides an approach to treat orthotopic tumor.

Background: Cardiovascular events secondary to stroke-collectively classified as stroke-heart syndrome-greatly impair the patient's prognosis, however its underlying mechanism has yet to be determined. To investigate the mechanism of central neuroinflammation and its effects on stroke-heart syndrome, a temperature-ultrasound responsive brain-targeted drug delivery system, DATS/MION-LPE, was synthesized to specifically study neuroinflammation in the mouse middle cerebral artery occlusion (MCAO) model.

Results: The specific polymer of DATS/MION-LPE can close the nanoparticle pores at 37 °C, restricting drug release in the circulation. After the nanoparticles were targeted to brains, the polymer can be cleaved under external ultrasound irradiation, reopening the nanoparticle pores and allowing drug release, therefore directly managing the neuroinflammation. After a stroke, a significant cerebral inflammation occurred, with elevated IL-1β and pyrin domain-containing 3 (NLRP3) inflammasome. Accordingly, significantly increased histone deacetylase 6 (HDAC6) and decreased sirtuin 1 (SIRT1) were observed. An antagonistic relationship between HDAC6 and SIRT1 was found, which can jointly regulate the cerebral NLRP3 expression. The systemic IL-1β and ATP levels were increased after the stroke, accompanied by a significant heart injury including contractile dysfunction, elevated IL-1β levels, and oxidative stress. Meanwhile, neuroinflammation can trigger sympathetic nervous overexcitation with associated heart damage. DATS/MION-LPE can targetedly effect on ischemic brain, exhibiting cerebral and cardiac protective effects including downregulated cerebral NLRP3 and HDAC6 expressions, upregulated SIRT1 expressions in brain, reduced IL-1β and ATP in circulation, and alleviated cardiac impairment.

Conclusion: This study introduced the key role of neuroinflammation in stroke-heart syndrome and first investigated the crucial HDAC6/SIRT1-NLRP3 circuit in this process. Heart injury secondary to stroke is mediated by neuroinflammation induced systemic inflammatory responses and sympathoexcitation. DATS/MION-LPE is a unique tool and effective therapeutic agent, which provides new insights into combinational heart and cardiac protection.

Organoids are "mini-organs" that self-organize and differentiate from stem cells under in vitro 3D culture conditions, mimicking the spatial structure and function of tissues in vivo. Extracellular vesicles (EVs) are nanoscale phospholipid bilayer vesicles secreted by living cells, rich in bioactive molecules, with excellent biocompatibility and low immunogenicity. Compared to EVs, organoid-derived EVs (OEVs) exhibit higher yield and enhanced biological functions. Organoids possess stem cell characteristics, and OEVs are capable of delivering active substances, making both highly promising for medical applications. In this review, we provide an overview of the fundamental biological principles of organoids and OEVs, and discuss their current applications in disease treatment. We then focus on the differences between OEVs and traditional EVs. Subsequently, we present methods for the engineering modification of OEVs. Finally, we critically summarize the advantages and challenges of organoids and OEVs. In conclusion, we believe that a deeper understanding of organoids and OEVs will provide innovative solutions to complex diseases.

Non-invasive imaging in the near-infrared region (NIR) offers enhanced tissue penetration, reduced spontaneous fluorescence of biological tissues, and improved signal-to-noise ratio (SNR), rendering it more suitable for in vivo deep tissue imaging. In recent years, a plethora of NIR photoresponsive materials have been employed for disease diagnosis, particularly acute kidney injury (AKI). These encompass inorganic nonmetallic materials such as carbon (C), silicon (Si), phosphorus (P), and upconversion nanoparticles (UCNPs); precious metal nanoparticles like gold and silver; as well as small molecule and organic semiconductor polymer nanoparticles with near infrared responsiveness. These materials enable effective therapy triggered by NIR light and serve as valuable tools for monitoring AKI in living systems. The review provides a concise overview of the current state and pathological characteristics of AKI, followed by an exploration of the application of nanomaterials and photoresponsive nanomaterials in AKI. Finally, it presents the design challenges and prospects associated with NIR photoresponsive materials in AKI.

Background: The production of β-lactamases is the most prevalent resistance mechanism for β-lactam antibiotics in Gram-negative bacteria. Presently, over 4900 β-lactamases have been discovered, and they are categorized into hundreds of families. In each enzyme family, amino acid substitutions result in subtle changes to enzyme hydrolysis profiles; in contrast, certain conserved sequences retained by all of the family members can serve as important markers for enzyme family identification.

Results: The SHV family was chosen as the study object. First, a unique 10-mer peptide was identified as SHV family's epitope by an approach of protein fingerprint analysis. Then, an SHV-specific magnetic epitope-imprinted gel polymer (MEI-GP) was prepared by an epitope surface imprinting technique, and its sorption behavior and recognition mechanism for template epitope and SHV were both elaborated. Finally, the MEI-GP was successfully applied to selectively extract SHV from bacteria, and the extracted SHV was submitted to MALDI-TOF MS for specific determination. By following this strategy, other β-lactamase families can also be specifically detected. According to the molecular weight displayed in mass spectra, the kind of β-lactamase and its associated hydrolysis profile on β-lactams can be easily identified. Based on this, an initial drug option scheme can be quickly formulated for antimicrobial therapy. From protein extraction to medication guidance reporting, the mean time to detection (MTTD) was less than 2 h, which is much faster than conventional phenotype-based methods (at least 16-20 h) and gene-based techniques (usually about 8 h).

Conclusions: This enzyme-specific detection strategy combined the specificity of epitope imprinting with the sensitivity of mass spectrometry, enabling β-lactamase to be selectively extracted from bacteria and clearly presented in mass spectra. Compared with other drug resistance detection methods, this technique has good specificity, high sensitivity (≤ 15 mg of bacteria), a short MTTD (less than 2 h), and simple operation, and therefore has a broad application prospect in clinical medicine.

Background: Porcine epidemic diarrhea virus (PEDV) infection and transmission pose a serious threat to the global swine industry. The search for a new host factor with anti-PEDV effect may be an effective potential target for the development of novel antiviral drugs. Interferon-induced transmembrane proteins (IFITMs) play a crucial role in the innate immune response triggered by viral infection, and it has been suggested that IFITMs can block the early stages of viral replication, but the mechanism of action is currently unclear. The current study sheds light on the role of IFITM1 in PEDV infection. Specifically, overexpression of IFITM1 suppresses PEDV proliferation in IPEC-J2 cells, while knockdown of IFITM1 has the opposite effect. Collectively, these findings underscore IFITM1's inhibitory role in PEDV infection, with critical implications for the residues and structural motifs within its CTD.

Results: The study demonstrates that IFITM1, an interferon-induced transmembrane protein, plays a critical role in the antiviral response against Porcine Epidemic Diarrhea Virus (PEDV). Notably: Overexpression of IFITM1 suppresses PEDV proliferation.IFITM1 co-localizes with PEDV virions in the cytoplasm surrounding the nucleus.Immunocolloidal gold electron microscopy reveals IFITM proteins embedded on the surface of PEDV virions.IFITM1 directly interacts with the N protein of PEDV.C-terminal domain mutations in IFITM1 compromise its inhibitory function against PEDV, with specific amino acid residues playing a pronounced role.These findings enhance our understanding of innate immunity and antiviral defense mechanisms, with potential implications for therapeutic strategies against PEDV infection.

Conclusions: The study establishes IFITM1 as a key player in the antiviral response against PEDV. Its inhibitory function, co-localization with virions, and interaction with the N protein provide valuable insights. Notably, the CTD mutations of IFITM1 have a fundamental impact on its modulatory action. These findings contribute to our understanding of innate immunity and antiviral defense mechanisms, with potential implications for therapeutic strategies against PEDV infection.

Objective: As research into preclinical rheumatoid arthritis (pre-RA) has advanced, a growing body of evidence suggests that abnormalities in RA-affected joint cartilage precede the onset of arthritis. Thus, early prevention and treatment strategies are imperative. In this study, we aimed to explore the protective effects of mesenchymal stem cell (MSC)-derived microvesicles (MVs) on cartilage degradation in a collagen-induced arthritis (CIA) mouse model.

Methods: A CIA mouse model was established to observe early pathological changes in cartilage (days 21-25) through histological and radiological examinations. On day 22, MSCs-MVs were intravenously injected into the mice with CIA. Radiological, histological, and flow cytometric examinations were conducted to observe inflammation and cartilage changes in these mice compared to the mice with CIA and the control mice. In vitro, chondrocytes were cultured with inflammatory factors such as IL-1β and TNFα to simulate inflammatory damage to cartilage. After the addition of MVs, changes in inflammatory levels and collagen expression were measured via Western blotting, immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), and quantitative PCR to determine the role of MVs in maintaining chondrocytes.

Results: MSC-MVs expressed vesicular membrane proteins (CD63 and Annexin V) and surface markers characteristic of MSCs (CD44, CD73, CD90, and CD105). In the early stages of CIA in mice, a notable decrease in collagen content was observed in the joint cartilage. In mice with CIA, injection of MSCs-MVs resulted in a significant reduction in the peripheral blood levels of IL-1β, TNFα, and IL-6, along with a decrease in the ratio of proinflammatory T and B cells. Additionally, MSC-MVs downregulated the expression of IL-1β, TNFα, MMP-13, and ADAMTS-5 in cartilage while maintaining the stability of type I and type II collagen. These MVs also attenuated the destruction of cartilage, which was evident on imaging. In vitro experiments demonstrated that MSC-MVs effectively suppressed the secretion of the inflammatory factors IL-1β, TNFα, and IL-6 in stimulated peripheral blood mononuclear cells (PBMCs).

Conclusions: MSCs-MVs can inhibit the decomposition of the inflammation-induced cartilage matrix by regulating immune cell inflammatory factors to attenuate cartilage destruction. MSC-MVs are promising effective treatments for the early stages of RA.

Background: The efficacy of mRNA-based vaccines and therapies relies on lipid nanoparticles (LNPs) as carriers to deliver mRNA into cells. The chemical structure of ionizable lipids (ILs) within LNPs is crucial in determining their delivery efficiency.

Results: In this study, we synthesized 623 alkyne-bearing ionizable lipids using the A³ coupling reaction and assessed their effectiveness in mRNA delivery. ILs with specific structural features-18-carbon alkyl chains, a cis-double bond, and ethanolamine head groups-demonstrated superior mRNA delivery capabilities. Variations in saturation, double bond placement, and chain length correlated with decreased efficacy. Alkynes positioned adjacent to nitrogen atoms in ILs reduced the acid dissociation constant (pKa) of LNPs, thereby hindering mRNA delivery efficiency. Conversion of alkynes to alkanes significantly enhanced mRNA delivery of ILs both in vitro and in vivo. Moreover, combining optimized ILs with cKK-E12 yields synergistic LNPs that showed markedly augmented mRNA expression levels in vivo.

Conclusions: Overall, our study provides insights into the structure-function relationships of ILs, providing a foundation for the rational design of ILs to enhance the efficacy of LNPs in mRNA delivery.

Gas therapy has emerged as a promising approach for treating cancer, with gases like NO, H₂S, and CO showing positive effects. Among these, NO is considered a key gas molecule with significant potential in stopping cancer progression. However, due to its high reactivity and short half-life, delivering NO directly to tumors is crucial for enhancing cancer treatment. NO-driven nanomedicines (NONs) have been developed to effectively deliver NO donors to tumors, showing great progress in recent years. This review provides an overview of the latest advancements in NO-based cancer nanotherapeutics. It discusses the types of NO donors used in current research, the mechanisms of action behind NO therapy for cancer, and the different delivery systems for NO donors in nanotherapeutics. It also explores the potential of combining NO donors with other treatments for enhanced cancer therapy. Finally, it examines the future prospects and challenges of using NONs in clinical settings for cancer treatment.