International Journal of Nanomedicine最新文献

Purpose: Human noroviruses (HuNoVs) are the main cause of non-bacterial acute gastroenteritis. Due to antigenic diversity, the discovery of ligands that can sensitively and specifically detect HuNoVs remains challenging. Limited by laboratory culture, no vaccines or drugs have been developed against HuNoVs. Here, we screened nucleic acid aptamers against the widespread HuNoV GII.4 and emerging HuNoV GII.17.

Methods: After ten rounds of sieving for HuNoV GII.4 and GII.17 virus-like particles (VLPs), eight ssDNA aptamers were generated and characterized for each genotype.

Results: Four of the eight aptamers generated for GII.4 VLP had dissociation constants (K_d) less than 100 nM, and all aptamers for GII.17 VLP had K_d less than 10 nM. All aptamers bound to their targets in VLP concentration-dependent manner. Two aptamers (AP4-2 and AP17-4) were selected for enzyme-linked aptamer sorbent assay (ELASA) and further analysis. Binding affinity was enhanced as the concentration of both aptamer and VLPs increased. The specificity of the aptamers was verified by ELASA and dot blotting. AP4-2 and AP17-4 were able to differentiate HuNoV from other diarrhea-causing pathogens or unrelated proteins (P < 0.0001). VLP/porcine gastric mucin (PGM) binding blockade assays revealed that AP4-2 and AP17-4 blocked the binding of HuNoV VLPs to PGM. VLP internalization inhibition assays showed that at a concentration of 0.5 µM, both AP4-2 and AP17-4 effectively inhibited attachment and internalization of HuNoV VLPs into 293T cell (P < 0.05). Cell viability assays confirmed that aptamers did not induce cellular toxicity.

Conclusion: AP4-2 and AP17-4 showed strong affinity and specificity for their target VLPs and represent promising candidates for HuNoV capture and detection. This is the first study to demonstrate that aptamers can effectively inhibit HuNoV VLPs from binding to or entering cells, thus providing a new concept for the treatment of HuNoVs.

Spinal cord injury (SCI) is a very destructive disease of the central nervous system that often causes irreversible nerve damage. Unfortunately, the adult mammalian spinal cord displays little regenerative capacity after injury. In addition, the glial scars and inflammatory responses around the lesion site are another major obstacle for successful axon regeneration after SCI. However, biomaterials are highly biocompatible, and they could provide physical guidance to allow regenerating axon growth over the lesion site and restore functional neural circuits. In addition, combined or synergistic effects of spinal cord repair can be achieved by integrating different strategies, including the use of various biomaterials and microstructures, as well as combining bioactive molecules and living cells. Therefore, it is possible to use tissue engineering scaffolds to regulate the local microenvironment of the injured spinal cord, which may achieve better functional recovery in spinal cord injury repair. In this review, we summarize the latest progress in the treatment of SCI by biomaterials, and discussed its potential mechanism.

Myocardial infarction (MI) is the leading cause of mortality from cardiovascular diseases. Rapid diagnosis and effective treatment are critical for improving patient prognosis. Although current diagnostic and therapeutic approaches have made significant progress, they still face challenges such as ischemia-reperfusion injury, microcirculatory disorders, adverse cardiac remodeling, and inflammatory responses. These issues highlight the urgent need for innovative solutions. Nanomaterials, with their diverse types, excellent physicochemical properties, biocompatibility, and targeting capabilities, offer promising potential in addressing these challenges. Advances in nanotechnology have increasingly drawn attention to the application of nanomaterials in both diagnosing and treating myocardial infarction. We summarize the pathophysiological mechanisms and staging of myocardial infarction. We systematically review the applications of nanomaterials in MI diagnosis, including the detection of biomarkers and imaging techniques, as well as in MI treatment, encompassing anti-inflammatory effects, antioxidant stress, inhibition of fibrosis, promotion of angiogenesis, and cardiac conduction repair. We analyze the existing challenges and provide insights into future research directions and potential solutions. Specifically, we discuss the need for rigorous safety assessments, long-term efficacy studies, and the development of robust strategies for translating laboratory findings into clinical practice. In conclusion, nanotechnology holds significant promise as a new strategy for diagnosing and treating myocardial infarction. Its potential to enhance clinical outcomes and revolutionize patient care makes it an exciting area of research with practical applications in real-world clinical settings.

Background: Quality control (QC) is an important element in ensuring drug substances' safety, efficacy, and quality. The dosing regimen for sEVs can be in the form of protein concentration or the number of particles based on the results of a series of quality controls applied as in-process control.

Methods: Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) were isolated from four independent umbilical cord samples and were characterized following the International Society for Cellular Therapy (ISCT) guidelines. Small extracellular vesicles (sEVs) were isolated separately from these four WJMSCs samples using the Tangential Flow Filtration (TFF) method and were characterized per Minimal Information for Studies of Extracellular Vesicles (MISEV2018) guidelines. Each isolated and concentrated sEV preparation was standardized and its purity was determined by the ratio of the number of particles to protein concentration.

Results: All the WJMSCs samples passed the Mesenchymal Stem Cells (MSCs) characterization QC tests. Qualitatively, EVs-positive markers (CD63 and TSG101) and intact bilipid membrane vesicles were detected in all the sEV preparations. Quantitatively, the protein and particle concentrations revealed that all the sEV preparations were "impure" with < 1.5 × 10⁹ particles/µg protein. Albumin was co-isolated in all the sEV preparations.

Conclusion: In short, all characterized and standardized individual and pooled sEV preparations were deemed "impure" due to albumin co-isolation using the TFF method. For therapeutic development, it is essential to report protein and particle concentrations in EV preparations based on these QC results.

Purpose: For the diagnosis of various diseases, simultaneous sensitive detection of multiple biomarkers using low sample volumes is needed. The purpose of the present research was to develop sensitive multiplex detection model of QD-based ELISA (QLISA), through the spectroscopic QD-analyte complex measurements in microvolume liquid droplets on a glass microslide.

Methods: QLISA was used for the detection of cartilage oligomeric matrix protein (COMP) and human growth hormone (hGH) as model analytes. The QLISA detection method included the formation of complexes consisting of analyte antigens, biotinylated antibodies and streptavidin-coated QDs. A specific immune-complex disassembling solution was used to dissociate analyte-antibody complexes from the bottom of the 96-well plate. After dissociation, the samples were diluted with PBS, and 2 µL transferred to a reusable glass slide for fluorescence (FL) scan.

Results: The alkaline immune-complex disassembling solution that most efficiently amplified QDs FL within a prolonged 17 h time was selected. Comparison of median fluorescence intensity (MFI) of 50 nM COMP, 25 nM COMP, and 5 nM COMP detection using QD655 with the dilution of the detached samples with PBS and without dilution resulted in significant MFI differences in all cases. The FL signal readouts from QD655 in the microvolume format were from 10 to 40 times stronger than those measured directly from a 96-well plate QLISAs. In duplex analysis, two analytes COMP and hGH were measured using different QD605 and QD525 in the same well. In the respectful 96-well plate QLISA format, two different analyte concentrations can be hardly distinguishable, but the transfer to micro-volumetric detection on the glass slide highly increased the signal strength according to green and red FL intensity of QDs.

Conclusion: Our method significantly enhances detection sensitivity, as compared to measured in parallel QLISAs in a 96 well plate format, enables multiplexing and may prove very valuable for samples of limited volumes.

Introduction: Photothermal therapy (PTT) is attracting increasing attention in treating atherosclerotic plaques. However, PTT can induce inflammatory responses, in turn stimulating the regeneration of atherosclerosis and hindering subsequent therapy.

Methods: In this paper, a multifunctional nanoparticle (Au NR@SiO₂/RSNO/DS, GSNPD) for the synergistic treatment of atherosclerosis through PTT and anti-inflammation effects was developed. The preparation and characterization of GSNPD, their cellular toxicity, photothermal conversion and targeted ablation efficiency, anti-inflammation and ROS scavenging effect, as well as the inhibition of foam cell formation were studied in vitro.

Results: The experimental results showed that the fabricated GSNPD NPs displayed positive effects on anti-atherosclerosis by pro-inflammatory macrophages ablation, NO production and ROS scavenging.

Discussion: GSNPD NPs were designed to effectively and accurately ablate pro-inflammatory macrophages by recognizing and targeting to SR-A overexpressed on the activated macrophages of arterial plaques via PTT, and simultaneous inhibit the PTT-induced inflammation through the laser-activated NO release in situ. This match of therapeutic agents and inhibitors not only achieves good therapeutic effects but also minimizes side effects as much as possible, which may provide an effective way for PTT-based treatment of atherosclerosis.

Purpose: Acne is a serious disfiguring follicular sebaceous gland disorder that negatively affects patients' quality of life and self-image. Chloramphenicol (CAM) is effective against Propionibacterium acnes and Staphylococcus aureus which cause acne, often used as a hospital preparation for acne treatment. However, because of its toxicity and poor water solubility, its use has been restricted. To overcome these limitations, the study focused on developing CAM-loaded binary ethosomes (CAM-BE) and incorporating them into a hydrogel system for transdermal delivery.

Methods: CAM-BE were prepared and characterized. Following incorporation of the selected formulation into the hydrogel, the formulation's skin-interaction was evaluated using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and confocal laser scanning microscopy (CLSM). Furthermore, a rat ear acne model was used to evaluate the formulation's in vivo anti-inflammatory efficacy and ex vivo skin permeability.

Results: The optimal formulation contained ethanol/propylene glycol ratios of 3:7 (w/w), exhibited particle size was 97.68 ± 4.9 nm, zeta-potential was -23.5 ± 1.3 mV, and encapsulation efficiency was 60.36 ± 2.12%. The BE hydrogel that was created showed persistent drug release. Additionally, it demonstrated an enhanced flow of 4.374 ± 0.12 μg/cm²/hour, permeability coefficient was 3.65 ± 0.09 cm/h×10^-3, and apparent skin deposition was 17.77 ± 1.13 μg/cm². CLSM and ATR-FTIR confirm that loading CAM into a binary ethosomes enables drugs to pass more easily through the stratum corneum. In vivo testing and histopathological analysis demonstrated that the CAM-BE hydrogel significantly inhibited swelling in the rat auricle, compared to both the free CAM hydrogel and adapalene hydrogel.

Conclusion: With their strong anti-inflammatory properties and improved skin penetration, binary ethosomes could be a viable new CAM delivery method. The new formulation was therefore seen as quite promising.

Background: A paramount issue in the realm of chronic wound healing among diabetic patients is the pervasive inflammatory response that persistently thwarts angiogenesis, thereby precipitating protracted delays in the healing process of such wounds. Employing zeolitic imidazolate framework-8 (ZIF-8) as a drug delivery platform, integrated within a temperature-sensitive injectable hydrogel, presents an intriguing strategy for the closure of various irregular wounds, modulation of inflammatory responses, and promotion of angiogenesis.

Methods: Herein, ZIF-8 loaded with curcumin (Cur) combined with methylcellulose/carboxymethyl chitosan (MCC) thermosensitive hydrogel was described. The assessment encompassed the temperature-sensitive properties, pH-responsive release, antimicrobial activity, and ROS scavenging capabilities of the MCC@ZIF-8@Cur hydrogel. A series of studies were conducted to explore its biocompatibility, pro-angiogenic effects, and macrophage M2 polarization induction. Additionally, a full-thickness skin defect model of diabetic rat was established to investigate the hydrogel's multifaceted efficacy in facilitating wound repair, mitigating inflammatory responses, and fostering angiogenesis.

Results: The thermosensitive MCC@ZIF-8@Cur hydrogel possess the attribute of being injectable and capable of in situ formation (gelation temperature of ≥ 28 °C), thereby establishing an effective physical barrier for a multitude of irregular wound profiles. The incorporation of ZIF-8@Cur confers the hydrogel with exceptional antibacterial properties and the capability to eliminate reactive oxygen species (ROS). Moreover, the pH-responsive MCC@ZIF-8@Cur hydrogel continuously releases Cur and Zn²⁺, mitigating inflammation, inducing M2 polarization of macrophages, and promoting angiogenesis. This creates a favorable immune microenvironment conducive to skin regeneration, thereby accelerating the healing of diabetic wounds. In vivo studies have demonstrated a markedly accelerated wound healing ratio in rats within the hydrogel group compared to the Control group (p<0.001). By the 14th day of wound healing, the MCC@ZIF-8@Cur hydrogel group achieved a remarkable healing ratio of 97.22%, considerably surpassing the Control group (72.98%), showcasing remarkable potential for treating diabetic wounds.

Conclusion: The findings demonstrate the successful creation of a temperature-sensitive hydrogel that exhibits remarkable antibacterial properties and ROS scavenging capabilities. This hydrogel effectively suppresses inflammatory responses, modulates the polarization of macrophages towards the M2 phenotype, and promotes angiogenesis, thus fostering a favorable immune microenvironment for skin regeneration. These attributes collectively augur promising prospects and applications in the healing of diabetic wounds.

Purpose: Metastatic non-small cell lung cancer (NSCLC) remains a global health threat, with patients facing inevitable disease progression despite standard-of-care therapy. Prior studies showed Platycodin D (PD)-induced cell cycle arrest and apoptosis in NSCLC via RNA regulatory network, yet elucidating PD's mechanisms in NSCLC progression is challenging in the real world.

Methods: Biological effects of PD on NSCLC cell lines A549 and PC-9 were assessed through in vitro assays, encompassing apoptosis, proliferation, colony formation, migration and invasion. MicroRNAs (miRNAs) expression was profiled, and their roles were investigated using miRNA mimics or inhibitors. Predicted miRNA targets were validated via dual-luciferase reporter assays and Western blotting following bioinformatic prediction. PD's metastatic inhibitory potential in NSCLC was evaluated in an in vivo lung cancer metastasis model. Furthermore, a homologous cell membrane-based PD delivery system was established to improve the biosafety and efficacy of PD in vivo.

Results: Hsa-miR-1246 was upregulated by PD treatment, and functional experiments demonstrated that the miR-1246-mimic enhanced PD's suppressive effects on NSCLC cell proliferation, colony formation, migration, and invasion, while the miR-1246-inhibitor abrogated these effects. Notably, dual-luciferase assays confirmed that hsa-miR-1246 directly targeted the 3' untranslated regions (3' UTRs) of Fucosyltransferase 9 (FUT9), modulating its expression. Moreover, the hsa-miR-1246/FUT9 axis regulated the phosphorylation level and expression of GSK3β protein. In vivo, PD encapsulated in homologous cell membranes mitigated tumor growth and migration in metastatic NSCLC mice with minimal side effects.

Conclusion: The application of PD prompted an increase in the expression levels of hsa-miR-1246 and a concurrent decrease in FUT9. Importantly, the therapeutic efficacy of PD in vivo was markedly enhanced through homologous cell delivery system. Collectively, this study revealed the potential utility of PD in the treatment of NSCLC progression.