Extracellular vesicles play an important role in intercellular communication, with the potential to serve as biomaterials for nanocarriers. Combining such extracellular vesicles and liposomes results in advanced drug delivery carriers. In this study, we attempted to fabricate hybrid vesicles using a membrane fusion method and incorporated an anticancer drug. As a result, we successfully prepared nanosized uniform hybrid vesicles and evaluated their physicochemical characteristics and intracellular uptake mechanisms via endocytosis in various cell lines. Compared to liposomes, the hybrid vesicles showed better physical properties and a relatively higher reduction in cell viability, which was presumably dependent on the specific cell type. These findings suggest that fusion-based hybrid vesicles offer a novel strategy for delivering therapeutic agents and provide insights into the types of extracellular vesicles that are useful in fabricating hybrid vesicles to develop an advanced drug delivery system.

Background/Objectives: Biodegradable polymers have emerged as promising platforms for drug delivery. Produced by microbiomes, polyhydroxyalkanoates (PHAs) offer excellent biocompatibility, biodegradability, and environmental sustainability. In this study, we report the surface functionalization of PHA-based nanoparticles (NPs) using the SpyTag–SpyCatcher system to enhance cellular uptake. Methods: Initial conjugation with mEGFP-SpyTag enabled visualization, followed by decoration with HER2-specific Affibody-SpyCatcher and/or TAT-SpyCatcher peptides. The prepared NPs retained a diameter of <200 nm and a negatively charged surface. Results: Affibody-functionalized NPs significantly enhanced internalization and cytotoxicity in HER2-overexpressing SK-BR-3 cells, whereas TAT-functionalized NPs promoted uptake across various cell types, independently of HER2 expression. Dual-functionalized NPs exhibited synergistic or attenuated effects based on the HER2 expression levels, highlighting the critical role of ligand composition in targeted delivery. Conclusions: The results of this study demonstrate that the SpyTag–SpyCatcher-mediated surface engineering of PHA NPs offers a modular and robust strategy for active targeting in nanomedicine.

Background/Objectives: Microbe-derived extracellular vesicles (MEVs) provide a biocompatible, naturally derived platform for drug delivery. Methods: We encapsulated doxorubicin in Lactobacillus plantarum-derived EVs and evaluated their ability at delivering doxorubicin to colorectal cancer cells in vitro. Endocytosis inhibitors were used to investigate the mechanisms by which the MEVs entered the cells. Results: The MEVs maintained structural stability under physiological conditions. Cellular internalization of doxorubicin-loaded MEVs involve clathrin/caveolae-dependent endocytosis, and dynamin- and clathrin-mediated pathways. Conclusions: These findings highlight the role of the microbe–cancer cell biointerface in mediating drug uptake and enabling intracellular delivery. The study supports the potential of MEVs as nanocarriers for anticancer drugs and provides mechanistic insights into the intracellular trafficking pathways that influence drug activity.

Photodegradation under ultraviolet irradiation significantly limits the efficacy of agrochemicals, leading to reduced field performance and increased environmental burden. Biodegradable polymer-based delivery systems have emerged as a promising strategy to address these limitations. Polyhydroxyalkanoate (PHA)-based microparticles (MPs) encapsulating pyraclostrobin (PYR), a model fungicide, were prepared using an emulsion–solvent evaporation method. The formulations were characterized by physicochemical properties, encapsulation efficiency, and release kinetics. Photostability under UV irradiation and antifungal activity against Aspergillus oryzae were systematically evaluated. As results, the MPs exhibited uniform size distribution and high encapsulation efficiency. Physicochemical analyses confirmed the physical incorporation of PYR within the PHA matrix without chemical alteration. The PHA matrix suppressed UV-induced photodegradation, enhancing photostability. In addition, the system demonstrated sustained release without an initial burst, with release rates dependent on polymer composition. This controlled release behavior resulted in prolonged antifungal activity. Based on these results, PHA-based microencapsulation provides an effective and sustainable strategy to enhance the stability and efficacy of photolabile agrochemicals, offering a versatile platform for advanced pesticide delivery.