Phospholipid-Anchored Ligand Conjugation on Extracellular Vesicles for Enhanced Cancer Targeting.

Extracellular vesicles (EVs) are recognized as potential candidates for next-generation drug delivery systems. However, the inherent cancer-targeting efficiency is unsatisfactory, necessitating surface modification to attach cell-binding ligands. By utilizing phospholipase D from Streptomyces in combination with maleimide-containing primary alcohol, the authors successfully anchored ligands onto milk-derived EVs (mEVs), overcoming the issues of ligand leakage or functional alteration seen in traditional methods. Quantitative nano-flow cytometry demonstrated that over 90% of mEVs are effectively modified with hundreds to thousands of ligands. The resulting mEV formulations exhibited remarkable long-term stability in conjugation proportion, ligand number, size distribution, and particle concentration, even after months of storage. It is further shown that conjugating transferrin onto mEVs significantly enhanced cellular uptake and induced pronounced cytotoxic effects when loaded with paclitaxel. Overall, this study presents a highly efficient, stable, cost-effective, and scalable ligand conjugation approach, offering a promising strategy for targeted drug delivery of EVs.

Hybrid nanovesicles derived from grapes and tomatoes with synergistic antioxidative activity.

Edible plants, rich in antioxidant compounds, offer defense against oxidative stress-induced cellular damage. However, the antioxidative benefits of edible plant-derived molecules are limited due to their instability, poor solubility, and low bioavailability. Plant-derived nanovesicles (PDNVs) have emerged as the next-generation nanotherapeutics and delivery platforms; yet, challenges including low purity, significant heterogeneity, insufficient enrichment of bioactive component and compromised therapeutic efficacy limit their application. In this study, a solvent-assisted vesicle hybridization technique was developed to engineer hybrid plant-derived nanovesicles (PDNVs), exemplified by grape and tomato-derived nanovesicles (GT-HNVs), which outperform their natural counterparts. The GT-HNVs demonstrated superior stability, enhanced radical-scavenging capabilities, and greater cellular uptake efficiency. Notably, GT-HNVs significantly reduced reactive oxygen species (ROS) levels and improved antioxidative enzyme activities in L-02 cells. Moreover, they mitigated oxidative stress-induced mitochondrial damage, restoring the membrane potential and morphology. Collectively, these findings underscore the therapeutic potential of hybrid PDNVs and offer an innovative strategy for their future research.

Development and Evaluation of Reconstructed Nanovesicles from Turmeric for Multifaceted Obesity Intervention.

The escalating prevalence of obesity poses significant health challenges due to its direct association with various diseases. Most existing medications, such as appetite suppressants and fat absorption inhibitors, suffer from limited effectiveness and undesirable side effects. Here, inspired by the versatile metabolic effects of turmeric, we developed a naturally derived nanoformulation of "Reconstructed Turmeric-derived Nanovesicles (Rec-tNVs)" for obesity treatment. Employing quantitative nanoflow cytometry, a four-orders-of-magnitude increase in curcumin content (∼108 molecules per particle) was identified in individual Rec-tNVs compared to their ultracentrifugation-isolated counterparts. Rec-tNVs, featuring highly aggregated curcumin arrangements and other coencapsulated bioactive compounds, demonstrated a dose-dependent lipid-lowering effect in mature 3T3-L1 cells by promoting lipolysis, suppressing lipogenesis, inducing adipocyte browning, and triggering apoptosis after internalization via multiple pathways. In vivo experiments revealed that Rec-tNVs alleviated obesity more effectively than free curcumin and achieved weight reductions of 18.68 and 14.56% through intragastric and subcutaneous delivery, respectively, in high-fat-diet mouse models over a four-week treatment period. These effects were attributed to targeted actions on adipose tissues and systemic impacts on metabolism and gut microbiota composition. Overall, this study underscores the multifaceted antiobesity efficacy of Rec-tNVs, and offers a promising paradigm for developing plant-derived nanovesicle-based therapeutics.