In this study, activated platelet‐derived vesicles (Act‐VEs) are developed as a novel hemostatic biomaterial. Spherical Act‐VEs (114.40 ± 11.69 nm in size) with surface charges of −24.73 ± 1.32 mV are successfully prepared from thrombin‐activated murine platelets with high surface expression of active glycoprotein IIb/IIIa (GP IIb/IIIa, also known as αIIbβ3) and P‐selectin. Although nanosized vesicles from resting platelets (VEs) and Act‐VEs showed similar sizes and surface charges, Act‐VEs formed much larger aggregates in the presence of thrombin and CaCl2, compared to VEs. After incubation with fibrinogen, Act‐VEs formed much denser fibrin networks compared to platelets or VEs, probably due to active αIIbβ3 on the surfaces of the Act‐VEs. After intravenous injection of the Act‐VEs, tail bleeding time and the blood loss are greatly reduced by Act‐VEs in vivo. In addition, Act‐VEs showed approximately sevenfold lower release of pro‐inflammatory interleukin‐1β (IL‐1β) during incubation for 4 days, compared to platelets. Taken together, the formulated Act‐VEs can serve as a promising hemostatic biomaterial for the efficient formation of fibrin clots without releasing pro‐inflammatory cytokine.
Here, as a proof of concept, hybrid vesicles (VEs) are developed from two types of cancer cells, MCF-7 and HeLa, for the dual targeting of the anticancer drug doxorubicin (Dox) to cancer cells via homotypic interactions. Hybrid VEs with a size of 181.8 ± 28.2 nm and surface charge of −27.8 ± 1.9 mV are successfully prepared by the fusion of MCF-7 and HeLa VEs, as demonstrated by the fluorescence resonance energy transfer assay. The hybrid VEs exhibit enhanced intracellular uptake both in MCF-7 and HeLa cells. Dox-encapsulated hybrid VEs (Dox-hybrid VEs) also exhibit promising anticancer and antiproliferative activities against MCF-7/multidrug-resistant cells and HeLa cells. In addition, compared to free Dox, the Dox-hybrid VEs exhibit low intracellular uptake and reduced cytotoxicity for RAW264.7 cells. Thus, hybrid VEs with dual-targeting activity toward two types of cancer cells may be useful for the specific targeting of anticancer drugs for improved anticancer effects with reduced nonspecific toxicity.
In this study, nanocomplexes composed of glycyrrhizic acid (GA) derived from the root of the licorice plant (
Glycyrrhiza glabra
) were formulated for the delivery of curcumin (CUR). Sonication of amphiphilic GA solution with hydrophobic CUR resulted in the production of nanosized complexes with a size of 164.8 ± 51.7 nm, which greatly enhanced the solubility of CUR in aqueous solution. A majority of the CURs were released from these GA/ CUR nanocomplexes within 12 h. GA/CUR nanocomplexes exhibited excellent intracellular uptake in human breast cancer cells (Michigan cancer foundation-7/multi-drug resistant cells), indicating enhanced anti-cancer effects compared to that of free CUR. In addition, GA/CUR nanocomplexes demonstrated high intracellular uptake into macrophages (RAW264.7 cells), consequently reducing the release of the pro-inflammatory cytokine tumor necrosis factor-α. Furthermore, GA/CUR nanocomplexes successfully reduced the levels of serum pro-inflammatory cytokines and splenomegaly in a rheumatoid arthritis model.
Infrared radiation is closely associated with skin diseases, such as photodermatosis and wrinkle formation, and erythema. 1,2 Infrared-A (IRA, 700-1400 nm) radiation constitutes approximately 30% of solar infrared radiation, which can penetrate down to the hypodermis and affect various types of cells in the skin. 3,4 However, the effects of IRA irradiation on skin cells are controversial, probably because of differences in IRA exposure conditions, such as the intensity of irradiation, exposure period, and temperature. 5,6 In addition, heat stresses during IRA irradiation on skin can induce various harmful effects, including the generation of reactive oxygen species (ROS) and apoptotic signals, making it difficult to understand the biological effects of IRA irradiation alone. 7,8 Hence, it is necessary to study the cellular effects of IRA irradiation alone under defined conditions of duration, frequency, and dose of IRA irradiation, as well as
In this study, a novel polyhistidine‐incorporated lipid nanoparticle (pHis/LNP) is developed for the delivery of therapeutic globotriaosylceramide (Gb3) synthase siRNAs using a microfluidic device with pHis as a biocompatible method of endosome escape. To inhibit the expression of Gb3 synthase, six siRNAs against Gb3 synthase are designed and an optimal siRNA sequence is selected. Selected Gb3 synthase siRNA is incorporated into pHis/LNP to prepare a spherical siRNA pHis/LNP with a size of 62.5 ± 1.9 nm and surface charge of −13.3 ± 4.2 mV. The pHis/LNP successfully protects siRNAs from degradation in 50% serum condition for 72 h. Prepared pHis/LNP exhibits superior stability for 20 days and excellent biocompatibility for A549 cells. After treatment with fluorescence‐labeled LNPs, dotted fluorescent signals are co‐localized with Lysotracker in cells with LNPs, whereas strong and diffused fluorescence intensity is observed in cells with pHis/LNPs probably due to successful endosomal escape. The extent of Gb3 synthase gene silencing by siRNA pHis/LNP is greatly improved (6.0‐fold) compared to that by siRNA/LNP. Taken together, considering that the fabricated siRNA pHis/LNP exhibits excellent biocompatibility and superior gene silencing activity over conventional LNP, these particles can be utilized for the delivery of a wide range of therapeutic siRNAs.
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