Extracellular vesicles (EVs) are secreted by almost all cells. They contain proteins, lipids, and nucleic acids which are delivered from the parent cells to the recipient cells. Thereby, they function as mediators of intercellular communication and molecular transfer. Recent evidences suggest that exosomes, a small subset of EVs, are involved in numerous physiological and pathological processes and play essential roles in remodeling the tumor immune microenvironment even before the occurrence and metastasis of cancer. Exosomes derived from tumor cells and host cells mediate their mutual regulation locally or remotely, thereby determining the responsiveness of cancer therapies. As such, tumor‐derived circulating exosomes are considered as noninvasive biomarkers for early detection and diagnosis of tumor. Exosome‐based therapies are also emerging as cutting‐edge and promising strategies that could be applied to suppress tumor progression or enhance anti‐tumor immunity. Herein, the current understanding of exosomes and their key roles in modulating immune responses, as well as their potential therapeutic applications are outlined. The limitations of current studies are also presented and directions for future research are described.
Illustration showing the fabrication process and test contents of electrospun gelatin nanofibers loaded with vitamins A and E as wound dressing materials in this paper.
To obtain wound dressings which could be removed easily without secondary injuries, we prepared thermoresponsive electrospun fiber mats containing poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA). Blend fibers of PDEGMA and poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL) were fabricated via electrospinning, and analogous fibers containing the antibiotic ciprofloxacin (CIF) were also prepared. Smooth cylindrical fibers were obtained, albeit with a small amount of beading visible for the ciprofloxacin-loaded fibers. X-ray diffraction showed the drug to exist in the amorphous physical form post-electrospinning. The composite fibers showed distinct thermosensitive properties and gave sustained release of CIF over more than 160h in vitro. The fibers could promote the proliferation of fibroblasts, and by varying the temperature cells could easily be attached to and detached from the fibers. Antibacterial tests demonstrated that fibers loaded with ciprofloxacin were effective in inhibiting the growth of E. coli and S. aureus. In vivo investigations on rats indicated that the composite PDEGMA/P(LLA-CL) fibers loaded with CIF had much more potent wound healing properties than a commercial gauze and CIF-loaded fibers made solely of P(LLA-CL). These results demonstrate the potential of PDEGMA/P(LLA-CL)/ciprofloxacin fibers as advanced wound dressing materials.
Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). It is proposed that inhibiting this interaction can be promising in treating COVID‐19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV‐ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S‐palmitoylated by zinc finger DHHC‐Type Palmitoyltransferase 3 (ZDHHC3) and de‐palmitoylated by acyl protein thioesterase 1 (LYPLA1), which is critical for the membrane‐targeting of ACE2 and their EV secretion. Importantly, by fusing the S‐palmitoylation‐dependent plasma membrane (PM) targeting sequence with ACE2, EVs enriched with ACE2 on their surface (referred to as PM‐ACE2‐EVs) are engineered. It is shown that PM‐ACE2‐EVs can bind to the SARS‐CoV‐2 S‐RBD with high affinity and block its interaction with cell surface ACE2 in vitro. PM‐ACE2‐EVs show neutralization potency against pseudotyped and authentic SARS‐CoV‐2 in human ACE2 (hACE2) transgenic mice, efficiently block viral load of authentic SARS‐CoV‐2, and thus protect host against SARS‐CoV‐2‐induced lung inflammation. The study provides an efficient engineering protocol for constructing a promising, novel biomaterial for application in prophylactic and therapeutic treatments against COVID‐19.
The objective of this work was to prepare a novel filament with good biocompatibility and mechanical performance which can meet the demands of surgical sutures. Bacterial cellulose nanocrystals (BCNCs) were used to reinforce regenerated chitin (RC) fibers to form BCNC/RC filaments. Mechanical performance measurements demonstrated that the strength of the BCNC/RC filament was increased dramatically over the RC analogue. A yarn made of 30 BCNC-loaded fibers also achieved satisfactory mechanical performance, with a knot-pull tensile strength of 9.8±0.6N. Enzymatic degradation studies showed the BCNC/RC materials to have good biodegradability, the rate of which can be tuned by varying the concentration of BCNCs in the yarn. The RC and the BCNC/RC materials had no cytotoxicity and can promote cell proliferation. In vivo experiments on mice demonstrated that suturing with the BCNC/RC yarn can promote wound healing without obvious adverse effects.
Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 ± 0.15 and 82.6 ± 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.
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