Search Results (319)

Cutaneous leishmaniasis remains a major therapeutic challenge due to drug toxicity, resistance, and limited efficacy against intracellular parasites. This study evaluated the therapeutic potential of nanoformulated Walterinnesia aegyptia (WA) venom using hyaluronic acid-based (WA-HA) and silver-based (WA-Ag) nanoparticles. Nanoparticles were synthesized and characterized by scanning and transmission electron microscopy and energy-dispersive X-ray spectroscopy. The antipromastigote activity of crude WA venom was assessed by MTT assay, and apoptosis induction was analyzed using Annexin V-FITC/propidium iodide flow cytometry. In vivo efficacy was evaluated in BALB/c mice infected with Leishmania major, with outcomes assessed by lesion progression, biochemical markers, histopathology, and PCR-based parasite detection. WA venom exhibited potent dose-dependent cytotoxicity (IC50 = 26.73 µg/mL) and induced predominantly apoptotic cell death. In vivo, nanoformulated WA significantly enhanced therapeutic outcomes compared with crude venom, with WA-HA achieving near-complete lesion resolution comparable to Amphotericin B. Treatment also reduced parasite burden, normalized liver enzyme levels, and restored hepatic and splenic architecture. These findings demonstrate that nanocarrier-based delivery markedly improves the therapeutic performance and systemic safety of WA venom, highlighting its potential as a promising nanotherapeutic strategy for cutaneous leishmaniasis. Full article

HIV-associated neurocognitive disorders (HAND) arise from HIV infection of the central nervous system, resulting in chronic neuroinflammation and progressive neuronal damage that impair cognitive, motor, and behavioral functions. Clinically, HAND encompasses a spectrum of neurological impairments ranging from asymptomatic neurocognitive impairment to severe HIV-associated dementia. Despite the widespread use of combination antiretroviral therapy (cART) and significant improvements in the life expectancy of people living with HIV, HAND remains prevalent and continues to pose a major clinical challenge. One of the primary limitations of cART is the limited penetration of many antiretroviral drugs across the blood–brain barrier (BBB), thereby allowing the persistence of viral reservoirs within the CNS and contributing to sustained neuroinflammation and neuronal damage. To address these challenges, novel nanotherapeutic strategies have been developed to enhance the delivery of antiretroviral agents to the brain. These approaches include targeted delivery systems and the co-delivery of therapeutics across the BBB through mechanisms such as receptor-mediated transcytosis and other transport pathways. In this review, we discuss the pathophysiological challenges associated with HAND and recent advances in nanotherapeutic approaches designed to improve treatment efficacy. We also discuss the current state of the art in vitro and in vivo models used to test the efficacy of these advanced therapeutics. Finally, we outline the remaining challenges and future prospects for the development of nanotherapeutics to improve the treatment of HAND. Full article

Chronic cutaneous wounds and traumatic skin injuries remain a major clinical challenge, characterized by dysregulated healing phases, high susceptibility to microbial infection, and suboptimal response to conventional therapies. Stem cell-derived exosomes (SC-Exos) have emerged as a paradigm-shifting, cell-free nanotherapeutic platform that harnesses the paracrine secretome of stem cells while avoiding the immunological and proliferative complications inherent to direct cell transplantation. Exosomes derived from diverse stem cell sources orchestrate multifactorial wound repair by modulating key cellular signaling cascades and transcriptomic programs that collectively regulate inflammation, angiogenesis, re-epithelialization, extracellular matrix (ECM) remodeling, and scar formation. Beyond their intrinsic regenerative capacity, SC Exos can be engineered using direct strategies (cargo loading, surface modification, biomaterial integration, and conjugation) and indirect approaches (genetic engineering, pretreatment, and preconditioning of parental cells), thereby enabling spatially controlled and temporally sustained exosome release at wound sites with enhanced bioavailability and therapeutic efficacy. In parallel, biomaterial-assisted delivery platforms, including hydrogels, scaffolds, and nanofibers, enhance exosome retention, stability, and controlled-release profiles within the wound microenvironment, thereby further potentiating tissue repair. This review provides a comprehensive overview of recent advances in SC Exos for wound healing and skin regeneration. We first summarize exosome biogenesis, molecular composition, and the distinctive characteristics of exosomes derived from different stem cell sources, along with preclinical evidence supporting their efficacy in cutaneous repair. We then critically examine exosome engineering strategies and biomaterial-integrated delivery systems that augment and fine-tune therapeutic outcomes. Finally, we discuss the current status of clinical trials of SC Exo-based therapies, key manufacturing and regulatory challenges, and future directions for translating these nanoscale, cell-free therapeutics into advanced, personalized wound management. Full article

Background/Objectives: Breast cancer remains a leading cause of cancer-related mortality worldwide, primarily due to the systemic toxicity and drug resistance associated with conventional doxorubicin (DOX) therapy. To overcome these limitations, we developed and optimized a novel cationic-ionizable lipid nanoparticle platform, QTPlus, for the co-delivery of DOX and siRNA targeting fibroblast growth factor 2 (siFGF2). Methods: The study evaluated the physicochemical properties, cellular uptake, gene regulation, apoptosis induction, and in vivo antitumor efficacy and safety of QTPlus-DOX-siFGF2 in breast cancer models. Results: QTPlus nanoparticles based on the A-066 formulation achieved uniform particle size (~218 nm), low polydispersity (PDI 0.164–0.214), and high encapsulation efficiencies (DOX: 49.56 ± 0.15%; siFGF2: 77.66 ± 1.30%). In vitro release studies revealed a robust pH-responsive profile, characterized by sustained stability at physiological pH (7.4) and rapid burst release at acidic endosomal pH (5.5). In MCF-7 and MDA-MB-231 cells, QTPlus-DOX-siFGF2 significantly enhanced cellular uptake, downregulated FGF2 (0.639-fold) and VIM (0.373-fold), and upregulated CASP3 (3.364-fold in siFGF2 group) and BRCA1 (4.041-fold). Flow cytometry showed markedly increased apoptosis (78.5% vs. 42.65% for QTPlus-DOX alone). In the MDA-MB-231 xenograft model, QTPlus-DOX-siFGF2 achieved 65.87% tumor growth inhibition with stable body weights and favorable trends in cardiotoxic biomarkers. Conclusions: These results demonstrate that QTPlus enables effective co-delivery of DOX and siFGF2, producing synergistic antitumor effects through apoptosis induction and suppression of epithelial–mesenchymal transition while improving the safety profile. QTPlus-DOX-siFGF2 represents a promising nanotherapeutic strategy for breast cancer warranting further clinical development. Full article

Gastric cancer (GC) is one of the most aggressive malignancies with a dismal prognosis, late diagnosis, and limited therapy efficacy. Biologically, GC is associated with multiple barriers to therapeutic response including gastric mucosal layer, acidic tumor microenvironment (TME), high accumulation of extracellular matrix (ECM) components, and limited penetration depth of anticancer drugs into tumor tissue. Furthermore, inherent or acquired drug resistance associated with drug efflux transporters, deregulated autophagy, tumor heterogeneity, and cell survival pathways severely compromise treatment response. Nanotechnology has been widely used to develop next-generation nanotherapeutic delivery systems to overcome these biological barriers. Currently available nanoplatforms such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanocarriers have improved drug loading capacity, aqueous solubility, circulation time stability, tumor-targeted delivery, and sustained release of chemotherapeutics. Smart and stimuli-responsive nanocarriers can also take advantage of pathological hallmarks of tumors including low pH, redox potential, and overexpressed enzymes for enhanced selective delivery to the tumor site. Nanotherapeutics have also shown promise for co-delivery of multiple therapeutic agents to overcome drug resistance, manipulation of TME, and suppression of autophagy and apoptosis signaling pathways associated with drug resistance. This review discusses recent advances in nanotherapeutics for GC including approaches to overcome biological barriers and drug resistance and highlights translational gaps for clinical development. Full article

Wound healing in cosmetological and aesthetic surgery extends beyond tissue closure to achieving rapid regeneration, minimal scarring, and restoration of functional skin architecture. However, conventional wound care strategies inadequately regulate the complex wound microenvironment required for optimal cosmetic outcomes, leading to prolonged healing times and suboptimal aesthetic results, which can negatively impact patient satisfaction and increase the risk of complications. Phytochemicals exhibit multifunctional bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and pro-regenerative effects, but their clinical translation faces obstacles due to poor solubility, stability, and bioavailability. Nanotechnology-based delivery systems have emerged as a critical enabling strategy to overcome these limitations. This narrative review provides an updated, mechanistically integrated synthesis of phytochemical-loaded nanotherapeutics, including polymeric nanoparticles, nanohydrogels, nanofibers, and lipid- and vesicle-based systems, with a specific focus on their roles in modulating key wound-healing pathways, such as inflammation resolution, angiogenesis, collagen remodelling, and re-epithelialization. Evidence from preclinical studies consistently demonstrates that nano-enabled phytochemicals enhance therapeutic efficacy, improve skin penetration, and contribute to superior cosmetic outcomes, particularly by reducing fibrosis and scar formation. However, critical gaps remain, including limited high-quality clinical evidence, a lack of standardized formulation design, variability in reported outcomes, and unresolved concerns regarding long-term safety and regulatory translation. Taken together, the key insight of this review is that phytochemical-loaded nanotherapeutics represent a promising but still transitional strategy, biologically compelling at the preclinical level yet clinically under-validated. Bridging this gap requires rigorously designed clinical trials, quantitative outcome reporting, and balanced regulatory frameworks. Advancing these areas will be essential to translate nano-enabled phytochemicals from experimental systems into reliable, evidence-based solutions for cosmetological wound management. Full article

Acute kidney injury (AKI) presents a critical clinical challenge due to its rapid progression and lack of effective targeted therapies. The herbal combination of rhubarb and Salvia miltiorrhiza, a cornerstone of Traditional Chinese Medicine (TCM) for renal protection, shows promise, yet its bioactive components and mode of action remain incompletely understood. This study identifies and characterizes inherent nanoscale entities from this herbal pair as a novel nanotherapeutic platform. Self-assembled nanoparticles (designated RSNPs) were isolated from the ethanol extract via differential centrifugation. Comprehensive characterization revealed that RSNPs form stable nanostructures through spontaneous self-assembly, primarily driven by supramolecular interactions (e.g., π-π stacking and hydrogen bonding). UPLC-MS/MS quantification confirmed the co-assembly of multiple bioactive constituents within RSNPs. Network pharmacology and molecular docking initially predicted their synergistic action on AKI-related pathways. In a cisplatin-induced murine AKI model, RSNP administration markedly attenuated renal dysfunction and histopathological damage, mechanistically linked to the mitigation of oxidative stress (e.g., decreased MDA and increased SOD) and inflammation (e.g., downregulated TNF-α and IL-6). In vitro, RSNPs demonstrated enhanced cellular internalization and superior cytoprotection against cisplatin toxicity in renal tubular epithelial cells, significantly reducing apoptosis. These findings unveil that the therapeutic efficacy of the Rheum palmatum L.–Salvia miltiorrhiza Bunge pair is intrinsically embedded within its nanoscale architecture. RSNPs represent a new class of TCM-derived nanotherapeutics with a well-defined material basis and multimodal mechanisms, offering a promising strategy for AKI treatment. Full article

Multidrug-resistant (MDR) Salmonella enteritidis infections cause high mortality and devastating economic losses in poultry, pose severe threats to animal health and food safety, and create an urgent demand for effective antibiotic alternatives. Herein, we developed a cationic liposome-encapsulated bacteriophage endolysin Lys40 (designated Lys40-Lip), and systematically evaluated its therapeutic efficacy in a chick model challenged with Salmonella enteritidis strain S4. Recombinant Lys40 was encapsulated into cationic liposomes with an encapsulation efficiency (EE) of 34.83%. The resulting Lys40-Lip nanoparticles had a hydrodynamic diameter of 137.3 ± 4.1 nm, a high positive zeta potential of +42.5 ± 0.3 mV, and excellent stability, retaining 78.52% of its initial bactericidal activity after 56 days of storage at 4 °C. Following a three-day oral treatment in Salmonella enteritidis S4-infected chicks, Lys40-Lip significantly increased survival rates in a dose-dependent manner (72.22% to 88.89% for low-to-high dose vs. 44.44% in infected controls, p < 0.05) and reduced ileal Salmonella enteritidis S4 colonization by 28.8% compared to free Lys40. Histopathology revealed Lys40-Lip restored duodenal villus integrity and reduced jejunal and ileal inflammation. Serum cytokine analysis confirmed that Lys40-Lip effectively regulated the host inflammatory response, significantly downregulating the pro-inflammatory cytokines IL-1β and IL-6, and upregulating the anti-inflammatory cytokine IL-10. Crucially, liposomal encapsulation overcame the outer membrane barrier of Gram-negative bacteria via charge-driven fusion mediated by its high positive surface potential (+42.5 ± 0.3 mV), enabling targeted delivery of Lys40 without the need for EDTA or other outer membrane permeabilizers. Lys40-Lip significantly improved the therapeutic outcomes of avian salmonellosis via synergistic direct bactericidal activity, intestinal barrier protection and inflammatory response regulation, offering a promising nanotherapeutic strategy for the control of this disease in veterinary practice. Full article

Calcium peroxide nanoparticles (CaO₂ NPs) have recently attracted increasing attention as oxygen-generating nanomaterials with potential biomedical applications. Their ability to release molecular oxygen and reactive oxygen species (ROS) in aqueous environments enables modulation of hypoxic and oxidative microenvironments, which play critical roles in infection control, tumor progression, and tissue regeneration. Despite growing interest in oxygen-releasing biomaterials, the literature specifically addressing CaO₂ nanomaterials remains comparatively limited and fragmented, particularly when compared with the extensive body of work on calcium oxide-based systems. This review provides a comprehensive overview of CaO₂ nanoparticles, focusing on synthesis strategies, physicochemical properties, and emerging biomedical applications. Conventional bottom-up synthesis routes based on calcium salts, calcium hydroxide, and calcium oxide are critically compared, highlighting the influence of reaction parameters and stabilizing agents on particle size, morphology, crystallinity, and colloidal stability. Surface modification strategies, including polyethylene glycol, polyvinylpyrrolidone, and hyaluronic acid, are also discussed for their role in improving nanoparticle stability, regulating decomposition kinetics, and enhancing biocompatibility. The mechanisms governing oxygen and ROS generation are analysed in relation to antibacterial activity, hypoxia alleviation in tumor microenvironments, and oxygen-supplying biomaterials for tissue engineering and wound healing. In addition, key challenges associated with oxidative stress responses are discussed. Finally, the review outlines current limitations and perspectives regarding the clinical translation of CaO₂-based nanotherapeutic systems. Overall, this work aims to consolidate the currently dispersed knowledge on CaO₂ nanoparticles and provide a critical framework to guide future research in oxygen-releasing nanomedicine. Full article

Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer, posing challenges to modern oncology. Current treatments, including surgery, radiation, and chemotherapy (e.g., Temozolomide or TMZ), often fail due to the inevitable development of drug resistance. TMZ resistance remains a major therapeutic challenge for the reasons that it is the first-line treatment. Recent studies indicate a rising GBM tumour burden and a trend towards earlier age of onset. It highlights the urgent need for evidence-based policymaking and intensified research to address this most difficult-to-treat malignancy in clinical settings. Ferroptosis, a newly recognized type of controlled cell death induced by iron-dependent lipid peroxidation, has emerged as a potential approach to overcome apoptosis resistance and restore drug sensitivity in GBM. This mechanism is modulated by key molecules that can be specifically targeted to either enhance oxidative stress or inhibit antioxidant defences, ultimately leading to tumour cell death. This review conducts a meta-analysis of preclinical evidence to better understand the potential of activating ferroptosis as a key target for developing nanoparticles to resensitize TMZ-resistant GBM cells. Current evidence indicates that combining ferroptosis induction with strategically engineered nanocarrier systems can serve as a novel and effective therapeutic approach to overcome TMZ resistance and advance precision-based GBM treatment. Full article

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune system disorders and multiple organ damage. Current clinical treatment of LN requires a complex multi-drug combination, which is often associated with severe side effects and low patient compliance. The aim of this study was to design a self-nanoemulsifying drug delivery system (SNEDDS) co-loading total glucosides of Paeonia (TGP) and dihydroartemisinin (DHA) to increase the solubility of the drug as well as achieve synergistic anti-inflammatory and immunomodulatory effects for LN therapy. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict the core therapeutic targets and related signaling pathways. The SNEDDS co-loaded with TGP and DHA was optimized via central composite design response surface methodology (CCD-RSM). Its physicochemical properties, particle size and the polydispersity index (PDI) of the optimized formulation were characterized. In vivo therapeutic efficacy was evaluated in MRL/lpr mice by measuring disease-related indicators (urinary protein, serum ANA, and anti-ds-DNA) and inflammatory cytokines (TNF-α, IL-6, and IL-1β). Renal tissue pathology was also examined. All data were analyzed by one-way analysis of variance (ANOVA) with p < 0.05 considered statistically significant. The core therapeutic targets predicted with high relevance were AKT1, MAPK1, MAPK3, and RELA. The optimized SNEDDS achieved a high loading capacity of 16.11 ± 0.43 mg/g for TGP and 12.79 ± 1.33 mg/g for DHA, with a particle size of (25.84 ± 0.30) nm and PDI of (0.07 ± 0.02). In MRL/lpr mice, SNEDDS treatment significantly reduced urinary protein levels (p < 0.01), serum ANA (p < 0.01) and anti-ds-DNA titers (p < 0.01) compared with the model group. Additionally, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were markedly decreased (p < 0.05), and renal tissue damage was alleviated. Conclusions: The SNEDDS co-loaded TGP and DHA is a promising oral nanotherapeutic strategy for LN, offering synergistic anti-inflammatory and immunomodulatory effects. Full article

Neuroinflammation is a central hallmark of numerous neurological disorders, including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and spinal cord damage. Its persistent and dysregulated nature not only accelerates neuronal loss but also impedes endogenous repair, posing a major challenge for effective therapeutic intervention. Recent advances in nanobiotechnology have opened transformative opportunities to modulate neuroinflammation with unprecedented precision while simultaneously supporting neural regeneration. This review highlights emerging nanomaterial-based strategies including lipid-based, polymeric, inorganic nanoparticles designed to traverse the blood–brain barrier (BBB), deliver anti-inflammatory agents, modulate immune cell behavior, and attenuate glial activation. Extending beyond nanoparticle-based delivery systems, recent advances also emphasize the integration of nanomaterials into biomimetic architectures to provide structural and functional cues for neural repair. We further summarize how these functional nanostructured scaffolds, such as extracellular matrix (ECM) mimetic, nanofibrous and conductive hydrogels, are being leveraged in neural tissue engineering to direct stem cell fate, promote axonal outgrowth, and rebuild damaged neuroarchitectures. Moreover, pharmacokinetics, biodistribution, safety, clinical trials, regulatory considerations and limitations of nanotherapeutics in neurodegenerative diseases are discussed. By outlining the current progress, mechanistic insights, and translational challenges, this review underscores the potential of nanobiotechnology-enabled therapeutics to revolutionize the treatment of neuroinflammatory conditions and advance next-generation neural repair technologies. Full article

HIV-associated neurocognitive impairment persists despite combination antiretroviral therapy, largely driven by chronic microglial activation that sustains neuroinflammation and neuronal injury. Activated microglia contribute to HIV-associated brain pathology by releasing proinflammatory mediators that disrupt synaptic integrity and impair cognition. N-acetylaspartylglutamate (NAAG), an abundant neuropeptide that maintains glutamatergic homeostasis, is hydrolyzed by glutamate carboxypeptidase II (GCPII) to glutamate. We previously demonstrated that reduced brain and cerebrospinal fluid NAAG levels in people living with HIV correlate with cognitive impairment, and that pharmacological GCPII inhibition with 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) elevates brain NAAG and improves cognition in EcoHIV-infected mice. To enhance brain delivery and preferentially target activated microglia, we conjugated 2-PMPA to a generation 4 hydroxyl poly(amidoamine) (PAMAM) dendrimer (D-2-PMPA). Our findings demonstrate that D-2-PMPA achieves preferential microglial drug delivery, resulting in a >600% increase in cerebrospinal fluid NAAG levels. At doses 8.3-fold lower than free 2-PMPA, this formulation reversed EcoHIV-induced deficits in social interaction, novel object recognition, and fear-conditioned memory without altering locomotor activity or anxiety-like behavior. D-2-PMPA also restored prefrontal cortex synaptic density and preserved dendritic architecture. Together, these findings demonstrate that microglia-targeted GCPII inhibition represents a potent nanotherapeutic strategy to restore synaptic integrity and cognitive function in HIV-associated neurocognitive impairment. Full article

Background: Myocardial ischemic injury, encompassing acute myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, remains a major cause of cardiac morbidity and mortality worldwide, and is driven by interconnected molecular and cellular processes, including cardiomyocyte apoptosis, inflammatory activation, mitochondrial dysfunction, oxidative stress, and impaired angiogenesis. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a promising cell-free nanotherapeutic strategy for cardiac repair due to their ability to transfer bioactive molecules that modulate multiple signaling networks involved in myocardial survival and regeneration. This systematic review aimed to synthesize evidence on the mechanistic basis of MSC-derived exosome mediated cardioprotection in myocardial ischemic injury. Methods: A systematic search of Ovid MEDLINE, Scopus, and Web of Science was conducted to identify studies investigating the effects of MSC-derived exosomes on myocardial ischemic injury. Eligible studies included clinical and preclinical models of MI or I/R injury assessing functional, biochemical, and molecular outcomes. Results: Seven preclinical studies published between 2015 and 2025 met the inclusion criteria. Exosome administration consistently improved cardiac function, reduced infarct size, and preserved myocardial architecture. Biochemical analyses revealed decreased cardiac injury markers, alongside suppressed apoptosis, inflammation, and oxidative stress. Mechanistically, MSC-derived exosomes delivered regulatory miRNAs (e.g., miR-19a, miR-125b, miR-205, miR-294) and lncRNAs (HAND2-AS1) that modulated key signaling pathways including PI3K/Akt, JAK2/STAT3, HAND2-AS1/miR-17-5p/Mfn2, and HIF-1α/VEGF. These molecular effects collectively inhibited apoptotic and inflammatory responses, enhanced mitochondrial integrity, and promoted angiogenesis and myocardial repair. Conclusions: MSC-derived exosomes confer robust cardioprotection against myocardial ischemic injury through integrated anti-apoptotic, anti-inflammatory, antioxidant, and pro-angiogenic mechanisms. Their multifaceted bioactivity, low immunogenicity, and potential for targeted delivery highlight their potential as a next-generation nanomedicine for ischemic heart disease. Future studies should emphasize standardized exosome production, mechanistic profiling, and translational validation in large-animal and clinical models. Full article

Background: Diabetes mellitus is a global health challenge associated with chronic complications like diabetic nephropathy and diabetic foot infections. Diabetic nephropathy, mediated by hyperglycemia-induced activation of the polyol pathway, represents a primary cause of end-stage renal disease. Additionally, infections caused by multidrug-resistant bacteria like Enterococcus faecalis lead to amputations and contribute to morbidity in diabetic patients. Methods: In this study, we synthetized nitrogen-doped carbon dots (N-CDs) using succinic acid with either hexamethylenediamine (N-HCD) or ethylenediamine (N-ECD) and evaluated their potential therapeutic applications. Results: Both N-HCD and N-ECD demonstrated a significant reduction in aldose reductase (AR) and sorbitol dehydrogenase (SDH) in vitro, with a substantial reduction in polyol pathway enzymatic activity. Furthermore, these N-CDs exhibited antibacterial activity against E. faecalis in vitro. Conclusions: Taken together, our findings suggest that N-HCD and N-ECD represent promising candidates for addressing diabetes-related complications and warrant further investigation for potential drug delivery applications. Full article