RESUMO
Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by Group A Streptococcus and ImpA secreted by Pseudomonas aeruginosa, as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αVß3 on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
Assuntos
Vesículas Extracelulares , Fagocitose , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Fagocitose/imunologia , Humanos , Animais , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/metabolismo , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/imunologia , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/imunologia , Pseudomonas aeruginosa/imunologiaRESUMO
The aggregation of nanoscale zero-valent iron (nZVI) particles and their limited transport ability in environmental media hinder their application in environmental remediation. In this study, the Cr(VI) removal efficiency, transport performance, and toxicity of nZVI and bentonite-modified nZVI (B-nZVI) were investigated. Compared with nZVI, B-nZVI improved the removal efficiency of Cr(VI) by 10%, and also significantly increased the transport in quartz sand and soil. Increasing the flow rate can enhance the transport of nZVI and B-nZVI in the quartz sand columns. The transport of the two materials in different soils was negatively correlated with the clay composition. Besides, modification of nZVI by bentonite could reduce toxicity to luminous bacteria (Photobacterium phosphereum T3) and ryegrass (Lolium perenne L.). Compared with Fe-EDTA, the transfer factors of nZVI and B-nZVI were 65.0% and 66.4% lower, respectively. This indicated that although iron nanoparticles accumulated in the roots of ryegrass, they were difficult to be transported to the shoots. The results of this study indicate that B-nZVI has a strong application potential in in situ environmental remediation.