Plant-derived nanovesicles: Further exploration of biomedical function and application potential

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Cell-derived nanovesicles from mesenchymal stem cells as extracellular vesicle-mimetics in wound healing

Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles (EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes. To circumvent these challenges, bioinspired cell-derived nanovesicles (CDNs) that mimic EVs were obtained by shearing mesenchymal stem cells (MSCs) through membranes with different pore sizes. Physical characterisations and high-throughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs. Moreover, these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway, resulting in enhancement of cell proliferation, cell migration, secretion of growth factors and extracellular matrix proteins, which all promoted tissue regeneration. Of note, MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEG-fibrin scaffold and animal model, accelerating wound healing in vitro and in vivo. These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.

Polystyrene-b-poly (acrylic acid) nanovesicles coated by modified chitosans for encapsulation of minoxidil

Abstract In this work, polystyrene-b-poly (acrylic acid) (PS-b-PAA) nanovesicles were coated by modified chitosans aiming at studying its physicochemical parameters. The chitosan (CS) was chemically modified to add hydrophilic and/or hydrophobic groups, obtaining three modified chitosans. The PS-b-PAA nanovesicles were obtained by organic (1,4-dioxane) cosolvent method in water, resulting in nanovesicles with less than 150 nm of diameter (polydispersibility index - PDI at 90° = 0.106), measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and negative zeta potential (-37.5 ± 3.2 mV), allowing the coating of its surface with oppositely charged polysaccharides, such as the CS and the modified chitosans. The coating process was made by mixing the colloidal suspensions with the CS and the modified chitosans at specific ENT#091;CS-xENT#093;/ENT#091;PS-b-PAAENT#093; ratios (0.001 to 1.0 wt %) and measuring the change in size and surface charge by DLS and zeta potential. Upon reaching maximum adsorption, the zeta potential parameter was positively stabilized (+26.7 ± 4.1 mV) with a hydrodynamic diameter slightly longer (< 200 nm of diameter). The encapsulation efficiency (EE) of minoxidil, quantified by capillary electrophoresis, was 50.7%, confirming their potential as drug delivery carriers and the coating process showed the possibility of controlling the surface charge nature of these nanovesicles

Black phosphrous quantum dot (BPQD)-loaded erythrocyte membrane vesicles for phothothermal therapy in breast cancer / 国际生物医学工程杂志

Objective To investigate the method of preparing black phosphrous quantum dot (BPQD)-loaded erythrocyte membrane nanovesicles (BPQD-EMNVs), and to study its efficiency in photothermal therapy for breast cancer. Methods Fresh red blood cells (RBCs) of healthy mice were extracted to prepare erythrocyte membrane, and BPQD-EMNVs were prepared by sonication method. The morphology of BPQD-EMNVs was observed by a transmission electron microscopy. The particle size distribution was measured by a nano-particle size and Zeta potential meter. The encapsulation efficiency of BPQD was determined by inductively coupled plasma emission spectrometry. The uptake rate of BPQD-EMNVs was observed by a laser scanning confocal microscope. 4T1 tumor-bearing Balb/c mice were randomly divided into PBS, EMNVs, BPQD and BPQD-EMNVs groups, and the tumor sites were irradiated with 808 nm near-infrared light for 10 min after 4 hours of tail vein injection. The growth of the tumors was continually observed. Results The prepared BPQD-EMNVs have a regular spherical shape with an average particle diameter of 228 nm and an encapsulation efficiency of about 47％. Cellular uptake in vitro experiments showed that BPQD-EMNVs were rapidly taken up by 4T1 tumor cells. The results of animal in vivo experiments showed that BPQD-EMNVs had the highest enrichment after 4 h of injection at the tumor site, and BPQD-EMNVs could effectively kill tumor tissues after 10 min of 808 nm near-infrared light irradiation. Conclusions The BPQD-EMNVs are easy to prepare, and the prepared nanovesicles have good biocompatibility and photothermiotherapy effect, which is expected to be a promising method for breast cancer therapy.