International Journal of Nanomedicine最新文献

Purpose: Nanoplastics (NPs) are widespread environmental pollutants that pose risks to human health; however, risk thresholds for NPs accumulation in human tissues remain poorly defined. This study validates gold-core polystyrene nanoplastics (AuPS-NPs) as a quantifiable proxy for polystyrene nanoplastics (PS-NPs) to evaluate toxicity and bioaccumulation at environmentally relevant concentrations, with extrapolation to human health implications.

Methods: AuPS-NPs were synthesized with a gold core and polystyrene shell, characterized by transmission electron microscopy (TEM) and quantified by inductively coupled plasma mass spectrometry (ICP-MS). In vitro, human gastric adenocarcinoma (AGS) and human colorectal adenocarcinoma (Caco-2) cells were exposed to AuPS-NPs or PS-NPs to assess cytotoxicity, reactive oxygen species generation, and mitochondrial membrane depolarization. In vivo, BALB/c mice were orally exposed to AuPS-NPs (1 and 10 mg/L) for 98 days, followed by evaluation of intestinal accumulation, body weight, organ indices, and biomarkers of inflammation, lipid metabolism, energy metabolism, and oxidative stress. A toxicokinetic-toxicodynamic (TK-TD) model was developed to simulate NPs accumulation, dose-response relationships, and human risk thresholds.

Results: AuPS-NPs and PS-NPs showed comparable concentration-dependent cytotoxicity in vitro. In vivo, chronic AuPS-NP exposure caused intestinal accumulation, body weight reduction, increased organ indices, and biomarker perturbations including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), triglycerides (TG), total cholesterol (T-CHO), adenosine triphosphate (ATP), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). TK-TD modeling yielded a human intestinal toxicity threshold of 9.529 × 10⁵ particles/kg, providing a particle-based reference for risk extrapolation.

Conclusion: AuPS-NPs replicate PS-NPs toxicity and enable quantitative risk assessment. Chronic exposure may induce intestinal accumulation and systemic toxicity, underscoring the need for regulatory thresholds to mitigate nanoplastic risks.

Osteoporotic bone defects (OBDs), characterized by disrupted bone metabolic homeostasis, insufficient vascularization, and a persistent inflammatory microenvironment, exhibit poor intrinsic regenerative capacity and remain a pressing clinical challenge in orthopedic practice. Plant-derived exosomes (P-Exos)-a unique class of bioactive nanovesicles enriched in regulatory miRNAs, lipids, proteins, and phytoactive metabolites-have emerged as promising natural modulators capable of enhancing osteogenic differentiation, suppressing excessive osteoclast activity, promoting angiogenesis, and mitigating inflammation. Intelligent hydrogels, with their tunable physicochemical properties, high biocompatibility, and extracellular matrix-mimicking architecture, provide a versatile platform for stabilizing P-Exos and achieving controlled, spatiotemporally regulated release. This review systematically summarizes the biological characteristics of P-Exos and elucidates their roles in orchestrating osteoporotic bone repair. Particular emphasis is placed on the design principles of environmentally responsive hydrogels-including thermosensitive, pH-responsive, photocrosslinkable, and other stimuli-adaptive systems-and their capacity to efficiently encapsulate and precisely deliver P-Exos. Furthermore, the synergistic effects of P-Exos-hydrogel composites in modulating the osteoimmune microenvironment, reinforcing angiogenesis-osteogenesis coupling, and accelerating functional bone regeneration are highlighted. Finally, the review addresses the major challenges that impede clinical translation, including the lack of standardized large-scale production of P-Exos, incomplete pharmacokinetic profiles under hydrogel-mediated release, and limited long-term in vivo data. Overall, this work provides a comprehensive conceptual framework and technical perspective to guide the development of safe, efficient, and precision-engineered therapeutic strategies for the treatment of osteoporotic bone defects.

Spinal cord injury (SCI) is a central nervous system injury caused by external forces or pathological factors, and traumatic SCI is the most common. If not treated promptly, traumatic SCI can cause secondary injury and neuroinflammation, leading to the proliferation of glial cells and formation of glial scars. Clinically, SCI is usually treated with surgical intervention, pharmacological therapy, or rehabilitation. However, good outcomes cannot be guaranteed. Therefore, SCI repair remains a central focus in neurotraumatic injury research. With an in-depth study of stem cells in nerve injury repair, stem cells and exosomes secreted by them have brought new hope for SCI treatment. Exosomes secreted by stem cells are small nano-sized vesicles, approximately 30-150 nm in diameter, that contain lipids, proteins, and nucleic acids. They can cross the blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB) through the blood system, and the proteins or nucleic acid molecules they carry promote nerve repair. Existing studies have demonstrated that exosomes exert therapeutic effects on SCI through multiple mechanisms: miRNA-mediated modulation of inflammatory responses, promotion of axonal regeneration and angiogenesis, inhibition of glial scar formation and apoptosis, as well as regulation of target cell gene expression via signal transduction pathways mediated by their carried signaling molecules. Although exosome research has yielded promising results in animal models of SCI, significant challenges remain in their clinical translation. Future research should focus on optimizing exosome production, improving purity, elucidating their precise mechanisms of action, and advancing their clinical translational applications.

Purpose: Helicobacter pylori (H. pylori) infection, implicated in chronic gastritis, peptic ulcers, and gastric cancer, poses a significant global health burden exacerbated by increasing antibiotic resistance. Traditional intramuscular vaccines often yield limited mucosal immunity, necessitating the development of more effective vaccination strategies capable of robust mucosal and systemic responses. Here, we report a novel nanovaccine (RA-NVs) combining all-trans retinoic acid (RA) and recombinant urease subunit proteins (UreA/UreB), encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enhance protective immunity against H. pylori.

Methods: RA-NVs were synthesized via single emulsion-diffusion-evaporation, with antigens loaded onto the nanoparticle surfaces. Their physicochemical properties, antigen loading capacity, and stability were characterized. In vitro dendritic cell (DC) activation, antigen uptake, and gut-homing receptor expression (C-C chemokine receptor 9, CCR9) were assessed. In vivo distribution was examined using in vivo imaging system (IVIS). BALB/c mice were immunized intramuscularly, and subsequent mucosal (IgA) and systemic (IgG) antibody responses, cytokine profiles, T cell proliferation, and bacterial clearance upon H. pylori challenge were evaluated. Vaccine biosafety was assessed via histopathological and biochemical analyses.

Results: RA-NVs exhibited optimal size, surface charge, and sustained antigen and RA release. In vitro assays demonstrated efficient DC uptake, enhanced CCR9 expression, cytokine secretion (IL-6, IL-10, IL-15), and improved DC migration towards C-C motif chemokine ligand 25 (CCL25). In vivo, RA-NVs significantly elevated serum IgG and mucosal IgA antibodies, promoted CD4+ and CD8+ T cell activation, and elicited robust Th2/Th17-skewed responses. Notably, immunized mice exhibited significantly reduced gastric bacterial colonization and inflammation upon H. pylori challenge, alongside excellent safety profiles with minimal toxicity and organ damage.

Conclusion: The RA-adjuvanted nanovaccine effectively induces potent mucosal and systemic immunity via intramuscular administration, representing a promising strategy against mucosal pathogens such as H. pylori. This nanovaccine platform addresses key limitations associated with oral vaccination and with conventional intramuscular approaches that often yield limited mucosal immunity, offering an alternative for enhancing mucosal vaccine efficacy in mice; although a direct head-to-head comparison with an oral formulation remains to be established.

Purpose: The early, precise, and safe management of vulnerable atherosclerotic plaques (VAPs) remains a formidable clinical challenge. Here, we present a targeted nanotherapeutic approach in which osteopontin-targeted nanoparticles encapsulate luteolin (NPs-Lut) for the precise delivery and treatment of VAPs. This engineered system enables site-specific accumulation and sustained release of luteolin at plaque sites.

Methods: We innovatively constructed an osteopontin-targeted drug delivery system designed for vulnerable atherosclerotic plaques, in which luteolin and atorvastatin were successfully encapsulated. The system demonstrated sustained-release capability in vitro, and its biosafety and histocompatibility were comprehensively evaluated both in vitro and in vivo. Moreover, therapeutic efficacy was further assessed in ApoE^-/- mice, confirming its potential for treating atherosclerotic lesions.

Results: In vivo evaluation in ApoE^-/- mice demonstrated that NPs-Lut markedly outperformed atorvastatin-loaded nanoparticles (NPs-AST) in attenuating plaque-associated inflammation, alleviating endoplasmic reticulum stress and foam cell apoptosis, and enhancing plaque stability. Histological analysis revealed a significant reduction in plaque and necrotic core area, accompanied by increased fibrous cap thickness and collagen deposition. By improving the aqueous solubility and bioavailability of luteolin, NPs-Lut achieved potent therapeutic efficacy at low doses while minimizing systemic toxicity.

Conclusion: This work provides a robust and translationally promising nanoplatform for the precision treatment of VAPs, offering a novel strategy for safe and effective intervention in atherosclerotic cardiovascular disease.

The incidence and prevalence of autoimmune diseases are rising globally, presenting a significant health challenge. Current treatments focus on symptom management and immunosuppression, often resulting in side-effects such as increased infection risk and broad immunosuppression. Targeted immune modulation strategies, particularly through nanomedicines, offer promising advancements by enabling precise drug delivery and reducing systemic toxicity, risks, and pharmacokinetic issues. Nanocarriers, which are nanoparticles with drugs encapsulated, improve targeting to inflamed areas and lymphoid tissues, protecting therapeutic agents from degradation. Administration routes-intravenous, subcutaneous, intramuscular, and oral-offer distinct benefits for enhancing efficacy in treating autoimmune diseases. In this review, we explore autoimmune diseases and review the limitations of current treatment options. We also emphasize the importance of exploring various administration routes for innovative nanocarrier systems and discuss their effects on modulating immune responses and inducing immune tolerance in autoimmune diseases. In particular, we highlight numerous preclinical studies utilizing intravenous, subcutaneous/intramuscular, and oral nanocarrier formulations that demonstrate substantial improvements in therapeutic efficacy and dose reduction compared to conventional therapies, underscoring the translational potential of nanomedicines for autoimmune diseases. Finally, we discuss future research directions and challenges in the development of nanomedicines for autoimmune diseases.

Background: Sepsis-associated acute lung injury (SALI) has high mortality, largely driven by a damaging cycle of oxidative stress and inflammation, with a lack of effective treatments. To address this, a novel biomimetic nanodrug was developed. It uses an amphiphilic copolymer (PT) to encapsulate the antioxidant/anti-inflammatory agent carnosic acid (CA), forming PT@CA micelles. These micelles are then coated with M2 macrophage membranes (MM) to create MM@PT@CA. Compared to traditional liposomes, the macrophage membrane has better inflammatory targeting and biological safety.

Methods: The PT copolymer was synthesized by grafting thioctic acid onto polylysine. CA was encapsulated via anti-solvent precipitation to form PT@CA, which was subsequently coated with M2 macrophage membranes via co-extrusion to yield the final bionic nanomicelle, MM@PT@CA. The system's ROS-responsive drug release, antioxidant, and antibacterial activities were characterized. Its biocompatibility, ability to scavenge cellular ROS, anti-inflammatory effects, and promotion of M2 macrophage polarization were assessed in vitro. Therapeutic efficacy was further evaluated in a mouse model of sepsis-induced lung injury.

Results: MM@PT@CA demonstrated significant multifunctional efficacy across a series of experiments. In vitro, it scavenged DPPH and ABTS radicals by 74.07% and 91.47%, respectively, and inhibited the growth of Staphylococcus aureus and Escherichia coli. It was efficiently taken up by cells and accumulated at inflammatory sites. Moreover, it exhibited excellent biocompatibility, remarkably restoring cell viability under oxidative stress from 48.70% to 93.85% while down-regulating pro-inflammatory factors. In vivo, MM@PT@CA treatment reduced apoptosis from 28.79% to 5.49%. Notably, the progression of SALI was effectively halted, which was attributed to its ability to modulate macrophage polarization and inhibit the pro-inflammatory cytokine storm.

Conclusion: The developed bionic nanomicelle targets inflammation, combats infection and oxidative stress, and ultimately alleviates SALI. These features highlight MM@PT@CA promising therapeutic potential for the treatment of SALI.

Purpose: This study aims to develop a quercetin-loaded nanoparticles (QNP) with enhanced brain delivery capacity, which enables efficient delivery of quercetin to target brain regions under the guidance of borneol for the treatment of depression.

Methods: We prepared QNP via the thin-film dispersion method and characterized them by particle size, polydispersity index (PDI), zeta potential, morphology, release profile, and stability. Subsequently, a suite of models and assays including hemolysis test, cellular CCK-8 assay, cellular uptake experiment, and lipopolysaccharide (LPS) induced BV2 cell stress model were employed to comprehensively assess the antidepressant activity of QNP. Finally, we validated the in vivo antidepressant effect of QNP using an established depression mouse model.

Results: QNP exhibit a spheroidal shape with favorable particle size, PDI, and zeta potential. They have high encapsulation efficiency and exhibit sustained drug release capability. QNP remain stable in serum and saline solution. They maintain stability after 30 days of storage at room temperature. Results from the hemolysis test and cellular CCK-8 assay preliminarily suggested that QNP had a favorable safety profile. Additionally, cellular uptake experiments showed that the uptake rate of QNP by cells was nearly twice that of the quercetin. Assays using corticosterone- and hydrogen peroxide-induced PC12 cell injury models demonstrate that QNP exert a concentration-dependent cytoprotective effect. In the LPS-induced BV2 cell stress model, QNP exhibit superior inhibitory activity against NO and ROS compared with Qu. They also significantly inhibit IL-1β transcription. In vivo studies indicated that, compared with the first-line antidepressant fluoxetine, QNP alleviated depressive-like behaviors more effectively.

Conclusion: The lipid nanodrug delivery system QNP exhibit sustained drug release and enhanced cellular uptake. By virtue of safety and improved delivery efficiency, they multidimensionally augment the therapeutic efficacy of antidepressants. This is crucial for translating quercetin from a dietary supplement into a precision antidepressant.

The emergence of drug resistance is the major obstacle to the clinical application of sorafenib (SOR), which often leads to disease progression, recurrence, and even death in hepatocellular carcinoma (HCC) patients. Nanocomposite-mediated drug delivery enhances targeting precision and therapeutic utilization efficiency. Nanocomposites constructed by nanoparticles (NPs) and various therapeutic components have emerged as effective approaches to enhance HCC therapeutic efficacy. Designing based on the mechanisms underlying SOR resistance, specially engineered nanocomposites can be designed to overcome SOR resistance. This review aims to highlight the advantages of nanocomposites in overcoming HCC SOR resistance. First, the various SOR resistance mechanisms that have been identified so far are briefly outlined. Second, the construction methods and characteristics of nanocomposites designed to overcome SOR resistance are summarized and categorized according to different types of NPs. Subsequently, the roles and therapeutic effects of nanocomposites in SOR-resistant HCC are analyzed, primarily including remodeling the tumor microenvironment (TME), restoring normal epigenetic regulation, improving drug metabolism, and inhibiting abnormally activated signaling molecules and pathways. Finally, the advantages and disadvantages of nanocomposites used to reverse drug resistance are discussed, and their development direction in future research is prospected, which provide new approaches for developing advanced nanocomposites to overcome SOR resistance.

Purpose: Rapid and accurate detection of acute heart failure (AHF) enables effective treatment of HF. This study aimed to to establish a timely test using colloidal selenium for initial screening and risk assessment of HF in primary care settings and at home.

Methods: Colloidal selenium was synthesized by reduction of sodium selenite with vitamin C under ambient conditions. In order to improve the stability of colloidal selenium and the coupling efficiency of the antibody, a novel synthetic method to coat polyethylene glycol 20000 (PEG20000) and sodium dodecyl sulfate (SDS) on colloidal selenium was developed. In order to improve the detection performance of colloidal selenium test strips, the labeling conditions and construction processes were optimized by the controlled variable method, and finally the test strips were successfully prepared.

Results: PEG20000 and SDS modified colloidal selenium had a very low detection limit of 250pg/mL, which met the sensitivity criteria for the diagnosis of acute heart failure in the Chinese Guidelines for the Diagnosis and Treatment of Heart failure (2024) that NT-proBNP ≤300 pg/mL can exclude acute heart failure, and ≤125 pg/mL can exclude chronic heart failure.

Conclusion: The developed single-step immunochromatographic method utilizing PEG20000 and SDS-modified colloidal selenium demonstrates meaningful potential for the rapid and reliable detection of NT-proBNP in serum samples from clinical patients. The colloidal selenium immunochromatographic technique developed in this study was assessed from the aspect of material synthesis, and the conditions for the application of this test paper were screened to verify the high specificity of the test paper, which met the criteria of the Chinese Heart Failure Diagnosis and Treatment Guidelines 2024 for acute heart failure.