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.
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.
Cationic quaternary ammonium (QA) groups and reactive oxygen species as two main approaches for antibacterial study have been intensively studied. Herein, we report a multifunctional antimicrobial agent (porphyrin-POSS-OPVE, PPO), which combines bacterial membrane intercalation, high density of local QA groups, efficient energy transfer, significantly reduced aggregation, and high water solubility into one single molecule. The light-harvesting PPO contains multiple donor-absorbing arms (oligo( p-phenylenevinylene) electrolytes, OPVEs) on its globular periphery and a central porphyrin acceptor in the core by using three-dimensional nanocages (polyhedral oligomeric silsesquioxanes, POSSs) as bridges. The antiaggregation ability of POSS and the highly efficient energy transfer from multiple OPVE arms to porphyrin could greatly amplify singlet oxygen generation in PPO. Particularly, OPVEs with QA terminal chains were able to intercalate into Escherichia coli membranes, which facilitated O diffusion and bacterial cell membrane disintegration by QA groups. The increased local cationic QA charges in OPVE arms can also enhance the biocidal activity of PPO. Benefiting from these satisfactory features, PPO exhibits multiamplified antibacterial efficacy under a very low concentration level and white light dose (400-700 nm, 6 mW·cm, 5 min, 1.8 J·cm) to Escherichia coli (8 μM) and Staphylococcus aureus (500 nM). Therefore, PPO shows great potential for photodynamic antimicrobial chemotherapy at a much lower irradiation light dose and photosensitizer concentration level compared to previous reports.
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