Journal of Nanobiotechnology最新文献

The reconstruction of large bone defects remains a significant clinical challenge, primarily owing to the insufficient mitochondrial protection and osteogenic activity of conventional implants. Exosomes (EXOs) derived from mesenchymal stem cells have emerged as promising tools for bone repair. This study reports a mitochondria-targeted therapeutic strategy utilizing EXOs derived from bone marrow mesenchymal stem cells (BMSCs). On MitoQ incorporation, these EXOs (EXO-MitoQ, EM) exhibit the targeted scavenging of mitochondrial reactive oxygen species; moreover, on surface decoration with the nucleic acid aptamer Apt 19 S (EM-Apt), they show the enhanced recruitment and precise delivery of BMSCs. The engineered EXOs show robust BMSC-targeting specificity and mitochondrial protective efficacy. To optimize their regenerative microenvironment and biomechanical properties further, these functionalized EXOs are integrated onto a 3D-printed β-tricalcium phosphate scaffold coated with a small intestinal submucosa (SIS) hydrogel, forming a composite system (TCP/SIS@EM-Apt). In a rat calvarial defect model, this TCP/SIS@EM-Apt scaffold increased the BV/TV by 1.9-fold compared to TCP/SIS, due to the combination of multiple multifunctional therapeutic effects (anti-inflammatory, angiogenic, and osteogenic). The mitochondria-targeting strategy proposed in this study presents a promising solution for the reconstruction of large bone defects and offers a synergistic approach for addressing complex regenerative challenges.

Effective osseointegration requires successful interaction between an implant and the local bone and immune environments. Surface modification presents a promising strategy to enhance the biocompatibility and integration of titanium implants. Although emerging research on transition metal carbides and nitrides (MXenes) demonstrates their potential to improve implant integration by modulating macrophage behavior and osteogenesis, existing studies have not explored synergistic modification strategies or the specific molecular mechanisms linking immunomodulation to bone healing. To address this, we developed a novel alkali-etched MXene (AE-MXene) coating by integrating alkali etching with MXene nanosheet loading, creating a platform that simultaneously optimizes micro/nanoscale surface topography and bioactive functionality-a synergistic approach previously unreported for MXene-based implants. Through comprehensive in vitro and in vivo analyses, we demonstrate that the AE-MXene surface possesses potent antibacterial, anti-inflammatory, and pro-osteogenic properties. Notably, we reveal for the first time that AE-MXene activates the AMP-activated protein kinase (AMPK)-mechanistic target of rapamycin (mTOR) pathway in macrophages, significantly upregulating autophagy to drive enhanced osteogenesis and angiogenesis. These findings delineate a unique autophagy-mediated mechanism through which AE-MXene promotes osseointegration, distinguishing it from prior MXene implant studies and highlighting its therapeutic potential for immunomodulatory and antimicrobial applications.

Background: Lactobacillus plantarum (L. plantarum) is a probiotic bacterium with diverse health-promoting effects. Recent evidence suggests that these benefits are mediated by extracellular vesicles (EVs) secreted by the bacterium; however, the underlying molecular mechanisms in the context of pathogenic inflammation remain poorly understood.

Results: In this study, we employed super-resolution stochastic optical reconstruction microscopy to elucidate the molecular mechanisms of action of L. plantarum EVs by monitoring alterations in the ultrastructural integrity of cellular organelles in human dermal fibroblasts exposed to Staphylococcus aureus EVs. Pathogenic EV exposure induced characteristic inflammatory changes in organelle morphology. Remarkably, both pre- and post-treatment with L. plantarum EVs restored organelle morphology in a concentration- and time-dependent manner. Cytokine profiling showed selective suppression of interleukin (IL)-6 and IL-8 while preserving IL-10, indicating targeted immunomodulation. We identified nicotinamide adenine dinucleotide (NAD⁺) as a key bioactive cargo, with exogenous NAD⁺ treatment reproducing both structural and cytokine-restorative effects.

Conclusions: These findings establish NAD⁺-mediated organelle protection as a central mechanism through which probiotic EVs mitigate bacterial inflammation. By linking organelle integrity to inflammatory outcomes, our study highlights L. plantarum EVs as nanoscale therapeutic candidates for infection-driven inflammation.

Mesenchymal stromal cell (MSC)-based strategies hold promises for treating diabetic foot ulcers. However, the hostile microenvironment of the lesions characterized by hypoxia, oxidative stress, and chronic inflammation impairs the survival and efficacy of transplanted MSCs. Here, we developed a composite bio-dressing by integrating MSC spheroid (Sp) derived from human embryonic stem cells via trophoblast intermediates (T-MSC) with gelatin methacryloyl hydrogel (Gm) and polydopamine nanoparticles (Pn). The GmPn matrix exhibited excellent adaptability, adhesion, porosity, biodegradability, and biocompatibility. Compared to monolayer-cultured T-MSCs, T-MSC Sp with scalable production via hanging drop demonstrated greater resilience to hypoxia and enhanced the migration and tube formation of vascular endothelial cells by secreting higher levels of chemokines and growth factors, verified by RNA-Seq and cytokine array. Furthermore, the combination of T-MSC Sp with Pn provided superior antioxidant, cell protection, and inflammation-regulatory effects compared to either component alone. The integration of T-MSC Sp, Gm, and Pn resulted in a bio-dressing termed SpGmPn, which accelerated wound area closer compared to Sp alone, owing to the synergistic effects of its components in stage-dependent immunomodulation and enhanced tissue regeneration. Thus, SpGmPn represents a promising and scalable therapeutic strategy for enhancing diabetic wound repair beyond the capabilities of T-MSC Sp alone.

Background: 2E,4E-decadienoic acid (DDA) is an aliphatic compound with potent anti‑oomycete activity against Phytophthora nicotianae (Pn), a plant pathogen responsible for major agricultural losses. Mechanistic studies revealed that DDA targets mitochondria and requires intracellular delivery to exert its activity. To improve its stability and bioavailability, we developed a reactive oxygen species (ROS)-responsive, TAT‑peptide (P) ‑modified liposomal (Lipo) delivery system (DDA@P‑ROS‑Lipo) containing thioketal (TK) linkages that cleave under elevated ROS conditions during pathogen infection, enabling controlled and site‑specific release of DDA. The TAT peptide, as a cell‑penetrating moiety, markedly enhanced intracellular uptake.

Results: The resulting nanoparticles exhibited an average hydrodynamic diameter of approximately 112 nm and a high DDA encapsulation efficiency of 80.84%. They also demonstrated excellent photostability, making the formulation suitable for field application. The nanoscale size and strong affinity for tobacco leaf surfaces reduced the contact angle, thereby improving adherence and deposition. Compared with free DDA, the nanoformulation enhanced mycelial inhibition by 45% and achieved superior control of tobacco black shank disease in pot experiments. Both in vitro cytotoxicity and in vivo zebrafish toxicity assays confirmed the safety of the formulation.

Conclusion: This work presents a simple and effective strategy for the targeted delivery of anti‑oomycete agents. DDA@P‑ROS‑Lipo offers a green and efficient approach for plant disease management under controlled conditions, and future studies will explore its scalability and performance in field environments.

The efficacy of oral chemotherapy for colorectal cancer (CRC) is hampered by poor drug stability and absorption in the upper gastrointestinal tract, as well as inadequate targeting efficiency at tumor sites. To address these issues, we proposed a simple and biocompatible nanogel, which was co-assembled from chemotherapeutic drug 5-fluorouracil (5-FU), regenerated silk fibroin (SF) as a natural protein carrier, and metal ions (Ni²⁺/Cu²⁺). The obtained nanogel system exploited the coordination interactions among 5-FU, amino acid residues, and metal ions to form a multifunctional oral nano-drug system with excellent biocompatibility, high delivery efficiency, and superior tumor penetration capacity. Embedding this nanogel in the chitosan/alginate hydrogel enabled it to effectively traverse the gastrointestinal (GI) tract and accumulate at colorectal tumor sites. Furthermore, the multi-stimuli-responsive properties of SF-based nanogel facilitated tumor microenvironment-responsive drug release, while metal ion-mediated chemodynamic therapy synergistically amplified the chemotherapeutic efficacy of 5-FU. This nanogel system provides a facile and translational strategy for improving the therapeutic performance of CRC chemotherapy.

Temporary amelioration of immunosuppression following extrinsic stress-induced immunogenic signal release provides opportunities for immunotherapy improvement. However, therapeutics that fail to translate local stimulatory clues into ongoing systemic antitumor responses would in turn hijack the alleviated immune status toward tolerance, instead of immunity. Here, we constructed a tumor-activated precise dual-metabolic nanomodulator (RAISE) that induced extensive tumor cell death while supporting DCs functions, thus synergistically turning over tolerogenic tumor control and skewing an antitumor immunity. Sequentially responsive to tumor-overexpressing enzymes and high intracellular GSH, RAISE disintegrated in a self-destructive manner, which facilitated drug release and produced immunogenic tumor cell death associated with immunosuppression relief. Then, the regression of tolerogenic metabolism by RAISE replenished intratumoral CD103⁺ DCs, which further amplified T cell activation by enhancing antigen cross-presentation. Moreover, the blockade of indoleamine 2,3-dioxygenase activity restored the sensitivity of tumors to T cell immunity. Consequently, the cascade of immune activation helped to escape from the fate of tolerance and evolved into durable immune memory. RAISE exhibited efficient tumor control, and when combined with anti-PD-1 immunotherapy, RAISE inhibited lung metastasis, generated systemic immune responses, and induced immune memory. Taken together, RAISE can be utilized to trigger long-term systemic antitumor immunity for improving tumor immunotherapy.

Renal ischemia-reperfusion injury (RIRI) is a prevalent and damaging pathological process in clinical practice, significantly impairing renal recovery and long-term prognosis. The pathogenesis of IRI involves multiple factors, including oxidative stress, inflammatory activation, cell death pathways, and microcirculatory disturbances. Conventional therapies have limited efficacy targeting individual factors and fail to provide comprehensive intervention within the complex RIRI pathological network. Recently, nanoparticles-due to their excellent biocompatibility, targeting ability, and environment-responsive characteristics-have become promising tools for precise diagnosis and multimodal therapy in RIRI. This review systematically summarizes recent advances in nanoparticle-based strategies for RIRI, emphasizing their mechanistic roles in modulating key pathological processes. These mechanisms involve ROS scavenging to reduce oxidative stress, inhibition of NF-κB to suppress inflammation, stabilization of mitochondria to prevent apoptosis, regulation of ferroptosis, and restoration of microcirculatory function. Furthermore, we highlight the potential of nanoparticles in diagnostic applications, such as enhancing lesion-specific localization and molecular imaging accuracy through intelligent stimulus-responsive systems. The article also discusses major challenges in translating nanotechnology clinically, including in vivo stability, biosafety, and large-scale production. Finally, we outline future research directions, such as the development of smart responsive platforms, multi-target synergistic therapeutic systems, and strategies for remodeling the renal immune microenvironment. Overall, this work aims to establish a theoretical foundation to advance nanotechnology's clinical application and mechanistic understanding in RIRI management.

Pulmonary delivery provides a noninvasive route for systemic administration of biologics, yet efficient lung deposition and permeation across pulmonary barriers remain major challenges. In this study, morphology-engineered zinc oxide (ZO) biointeractive carriers were fabricated and evaluated as inhalable carriers for liraglutide (LG). Three distinct morphologies were obtained: smooth spherical ZO-1 (5-7 μm), spiky sea-urchin-like ZO-2 (5-8 μm with elongated ~ 3.5 μm tips), and compact spiky ZO-3 (1-3 μm with short ~ 1.3 μm tips). Particle image velocimetry (PIV) revealed morphology-dependent aerodynamic behaviors, where ZO-3 exhibited turbulence-driven dispersion favoring distal lung deposition. At the cellular level, ZO-3 demonstrated enhanced mucus penetration and reduced macrophage uptake, maintaining prolonged contact with the epithelial surface. Following intratracheal administration, LG@ZO-3 achieved bioavailability of ~ 60% relative to subcutaneous injection in healthy rats and ~ 51% in diabetic rats, far exceeding the < 2% oral bioavailability of semaglutide. These results suggest that morphology-controlled modulation of aerodynamic and biological interactions can overcome multiple pulmonary barriers, offering a promising strategy for effective inhalable delivery of peptide therapeutics.