الملخص
Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe3O4 nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.
الملخص
Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.
الملخص
Objective To investigate ultrahistopathological features of symmetrical acrokeratoderma.Methods Biopsy specimens were obtained from skin lesions and perilesional normalappearing skin of 6 patients with symmetrical acrokeratoderma,as well as from normal skin of 3 healthy volunteers.Then,these skin specimens were subjected to transmission electron microscopy (TEM).Results TEM showed obviously thickened stratum corneum,irregular morphology of keratinocytes and discontinuous cornified envelope.Aggregation and abnormal arrangement of keratin filaments occurred in all epidermal layers.Many vacuoles of different sizes were observed in the transitional zone between the stratum corneum and stratum granulosum.Hypogranulosis,abnormal shape and different sizes of keratohyalin granules,and reduction of membrane-coating granules were found in the stratum granulosum.Increased melanocytes with a large number of stage Ⅳ melanosomes in the cytoplasm were observed in the basal layers.Moreover,there was infiltration of a few lymphocytes in the superficial dermis.Perilesional normal-appearing skin tissues showed similar but milder ultrastructural changes.Conclusion Abnormal metabolism of keratins,epidermal differentiation complex proteins and lipids may exist in skin lesions of symmetrical acrokeratoderma,which may contribute to epidermal thickening and impairment of skin barrier function.
الملخص
Objective:To study the effect of membrane-coating on dissolution and stability of sirolimus ( SRL) dropping pills to prove the effect and rationality of the coating process. Methods:Opadry was used as the coating material for SRL dropping pills. Com-pared with those of uncoated SRL dropping pills, the dissolution and stability of membrane-coating SRL dropping pills were studied in vitro. Results:Compared with that of uncoated SRL dropping pills, the drug release amount of membrane-coating SRL dropping pills was lower (P0. 05). After the membrane-coating, the stability of SRL dropping pills was notable enhanced under high humidity (75% ± 5%) and strong light (4500lx ± 500lx) conditions, however, the stability showed no improved under high temperature(40℃ ± 2℃) condition. Conclusion: The membrane-coating can enhance the stability of SRL dropping pills without significant effect on drug release in vitro.
الملخص
Objectives: To reveal the morphological features of the stratum corneum lipids in hairless mouse epidermis. Methods: Ruthenium tetroxide and osmium tetroxide were compared as post fixative in the preparation of hairless epidermis for transmission electron microscopic examination. Results: Both reagents reveled characteristic membrane coating granules within the granular layer. Whereas, the transformation of the membrane coating granule contents into multiple lamellae at the interface between the granular and cornified layers and the persistence of these lamellae through all levels of the stratum corneum were demonstrated only by ruthenium tetroxide fixation. Conclusions: The distinctive patterning of the intercellular lamellae reflects the nonrandom organization of the stratum corneum lipids. In addition, the ruthenium tetroxide postfixation technique is a useful method in the investigation of the morphological features of the stratum corneum lipids.