Atherosclerosis is a key mechanism underlying the pathogenesis of cardiovascular disease, which is associated with high morbidity and mortality. In the field of precision medicine for the treatment of atherosclerosis, nanoparticle (NP)-mediated drug delivery systems have great potential, owing to their ability to release treatment locally. Cell-derived biomimetic NPs have attracted extensive attention at present due to their excellent targeting to atherosclerotic inflammatory sites, low immunogenicity and long blood circulation time. Here, we review the utility of cell-derived biomimetic NPs, including whole cells, cell membranes and extracellular vesicles, in the treatment of atherosclerosis.
Expansins are cell wall loosening proteins which generally play important roles as endogenous regulators in plants. Here we report a rice (Oryza sativa L.) b-expansin gene, OsEXPB2, which encodes a 28.6-kDa protein of 261 amino acids. Sequence alignment revealed that the N-terminal and C-terminal of OsEXPB2 share six discontinuous cysteine residues and four intermittent tryptophan residues, respectively. The OsEXPB2 promoter contains conserved root hair-specific elements. Subcellular localization assay revealed that OsEXPB2 was localized in the cell wall. Analysis of spatial and temporal expression patterns demonstrated that OsEXPB2 was predominantly expressed in root of rice. OsEXPB2 expression levels were up-regulated by abiotic stresses, such as phosphate or iron deficiency, and also suppressed by abscisic acid. A clear difference was observed between RNA interference (RNAi) lines and wildtype in root system architecture and plant height, and the suppression of OsEXPB2 resulted in a visible alteration of the width of the leaf blade. Anatomical analysis found that the cell size of root cortical cells in OsEXPB2-suppressed lines was significantly smaller than that of their counterparts in wild-type plants. Furthermore, cryo-scanning electron microscopy analysis showed that the development of root hair was suppressed in RNAi lines. All these results suggest that OsEXPB2 is a root-predominant gene with a key role in root-hair formation and has the potential to be utilized in transgenic root breeding to improve abiotic stress tolerance.
Rationale: As a potentially life-threatening disorder, cerebral ischemia-reperfusion (I/R) injury is associated with significantly high mortality, especially the irreversible brain tissue damage associated with increased reactive oxygen radical production and excessive inflammation. Currently, the insufficiency of targeted drug delivery and "on-demand" drug release remain the greatest challenges for cerebral I/R injury therapy. Bioengineered cell membrane-based nanotherapeutics mimic and enhance natural membrane functions and represent a potentially promising approach, relying on selective interactions between receptors and chemokines and increase nanomedicine delivery efficiency into the target tissues. Methods: We employed a systematic method to synthesize biomimetic smart nanoparticles. The CXCR4-overexpressing primary mouse thoracic aorta endothelial cell (PMTAEC) membranes and RAPA@HOP were extruded through a 200 nm polycarbonate porous membrane using a mini-extruder to harvest the RAPA@BMHOP. The bioengineered CXCR4-overexpressing cell membrane-functionalized ROS-responsive nanotherapeutics, loaded with rapamycin (RAPA), were fabricated to enhance the targeted delivery to lesions with pathological overexpression of SDF-1. Results: RAPA@BMHOP exhibited a three-fold higher rate of target delivery efficacy via the CXCR4/SDF-1 axis than its non-targeting counterpart in an in vivo model. Additionally, in response to the excessive pathological ROS, nanotherapeutics could be degraded to promote "on-demand" cargo release and balance the ROS level by p-hydroxy-benzyl alcohol degradation, thereby scavenging excessive ROS and suppressing the free radical-induced focal damage and local inflammation. Also, the stealth effect of cell membrane coating functionalization on the surface resulted in extended circulation time and high stability of nanoparticles.
Conclusion:The biomimetic smart nanotherapeutics with active targeting, developed in this study, significantly improved the therapeutic efficacy and biosafety profiles. Thus, these nanoparticles could be a candidate for efficient therapy of cerebral I/R injury.
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