Skin aging is commonly characterized by increased wrinkles, loss of elasticity, and hyperpigmentation, significantly affecting personal appearance and quality of life. Although botulinum toxin type A (BTX-A) has been widely applied in cosmetic anti-wrinkle treatments, its intrinsic cytotoxicity limits broader clinical applications. In this study, we developed a novel exosome-based BTX-A composite delivery system designed to synergize the anti-aging properties of exosomes with the wrinkle-reducing effects of BTX-A while reducing toxicity. Human adipose-derived mesenchymal stem cells were genetically modified via lentiviral transduction to overexpress Synaptic Vesicle Glycoprotein 2C (SV2C), the receptor of BTX-A, thereby producing SV2C-enriched functionalized exosomes (EXO^SV2C). These exosomes (2.0 × 10⁷ particles/mL) were incubated with BTX-A (3 U/mL) to generate the EXO^SV2C-BTX-A complex. In vitro, EXO^SV2C-BTX-A significantly promoted the proliferation and migration of human dermal fibroblasts and effectively alleviated D-galactose (D-gal)-induced cellular senescence and collagen type I loss. These effects were superior to those observed with either BTX-A or exosomes alone. In vivo, intradermal injection of EXO^SV2C-BTX-A for 28 days markedly suppressed D-gal-induced skin aging in 8-week-old male KM mice, as evidenced by reduced malondialdehyde levels in dermal tissue, enhanced collagen type I expression, and preserved skin structure. Notably, the composite exhibited significantly lower toxicity compared to free BTX-A. Collectively, these findings highlight EXO^SV2C-BTX-A as a promising exosome-mediated BTX-A delivery platform with enhanced anti-aging efficacy and improved biocompatibility, offering a potential therapeutic strategy for skin rejuvenation.

Alzheimer’s disease (AD) lacks effective disease-modifying therapies, and extracellular vesicles (EVs) derived from adipose-derived mesenchymal stromal cells (ADMSCs) have emerged as promising therapeutic candidates. In this study, we investigated the brain biodistribution and dose-dependent effects of intranasally administered ADMSC-EVs in female APP/PS1 mice, with age-matched wild-type mice and vehicle-treated transgenic mice serving as controls. EV biodistribution was assessed using PKH26 labeling, cognitive performance was evaluated using the Morris water maze, Y-maze, and novel object recognition tests, and hippocampal amyloid pathology and plasma AD-related biomarkers were analyzed. Intranasally delivered ADMSC-EVs rapidly reached multiple brain regions, including the hippocampus, improved learning and memory performance, and reduced hippocampal amyloid-β 1-42 (Aβ42) deposition and plaque burden. These effects followed a nonlinear dose–response pattern, with reduced efficacy at low doses and no additional benefits at high doses. Notably, partial behavioral and pathological benefits persisted after treatment cessation. Together, these findings show that intranasal ADMSC-EVs exert therapeutic effects in APP/PS1 mice and support the importance of dose optimization and post-treatment durability in the development of EV-based interventions for AD.

Sudden unexpected death in epilepsy (SUDEP) and long QT syndrome (LQTS) are severe disorders causing sudden death in the neurological and cardiovascular systems, respectively, and have traditionally been viewed as distinct clinical entities. However, their overlapping clinical phenotypes and partially shared genetic backgrounds suggest that, in a subset of patients, overlapping molecular mechanisms may contribute to neurocardiac vulnerability. This review systematically elucidates and bridges the potential mechanistic intersections between these two conditions at the level of ion channel dysfunction. It focuses on key shared ion channel genes, such as KCNQ1 , KCNH2 , and SCN5A , and analyzes how their variants may simultaneously induce neuronal hyperexcitability and cardiomyocyte repolarization abnormalities, thereby suggesting a potential risk-modifying framework of “cardio-cerebral ion channelopathies” in specific clinical scenarios. Additionally, this article discusses the significant implications of this shared mechanism for clinical practice, particularly in evaluating the cardiac safety of anti-seizure medications (ASMs), integrating genetic risk stratification, and developing future therapeutic strategies. By synthesizing and integrating existing evidence, this review aims to provide a broader pathophysiological perspective on the intrinsic links between SUDEP and LQTS, offering novel insights for interdisciplinary precision medicine.

The clinical management of spinal tumors presenting with acute spinal cord compression with consequent neural injury poses two concurrent challenges: achieving oncological control and preserving or restoring neurological function. Surgical decompression and chemoradiotherapy can relieve mechanical compression and reduce tumor burden, but they do not directly restore the damaged neural microenvironment. In recent years, extracellular vesicles (EVs) have emerged as promising cell-free nanotherapeutic candidates. Preclinical evidence suggests that they can cross the blood-spinal cord barrier and deliver functional biomacromolecules. This narrative review critically evaluates recent advances in EV-based interventions for spinal tumors and associated neural injury. To improve interpretive rigor, we distinguish evidence according to translational proximity, from human-derived data and orthotopic spinal tumor models to non-spinal tumor and non-neoplastic spinal cord injury models. We discuss how natural and engineered EVs may improve selective targeting, help overcome chemotherapy resistance, regulate neuroinflammation, and promote axonal regeneration. However, EV therapeutics for spinal tumors remain at an early preclinical stage. In spinal microenvironments that may contain residual tumor cells, EVs can exert double-edged effects, including off-target toxicity, pro-tumorigenic niche remodeling, and enhanced immune evasion. Scalable isolation, purification, and standardized potency assessment under international consensus frameworks remain major barriers. Dedicated tumor-bearing spinal models are therefore required to determine whether EV-based interventions can be developed into safe, viable, and personalized therapeutic approaches.