Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation.

BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

MicroRNA-144 silencing attenuates intimal hyperplasia by directly targeting PTEN.

BACKGROUND: Intimal hyperplasia contributed by phenotypic switching of vascular smooth muscle cell (VSMC) plays an important role in the pathogenesis of various cardiovascular diseases. MicroRNA-144 (miR-144) is recently reported to be implicated in the development of atherosclerosis. However, the individual role of miR-144 in VSMCs phenotypic modulation and intimal hyperplasia currently still remains unknown. METHODS AND RESULTS: Here we found that miR-144 expression was upregulated in carotid arteries with intimal hyperplasia that subjected to wire injury and the consistent results were obtained with dedifferentiated VSMCs upon platelet-derived growth factor-BB (PDGF-BB) stimulation. Loss-of-function study showed that miR-144 knockdown decreased the ability of VSMC proliferation tested by Brdu and CCK8, and reduced the migrate capability analyzed by Transwell, whereas increased the differentiated SMC marker gene expression examined by RT-PCR. The above results were reversed by miR-144 overexpression. Mechanistically, we have demonstrated that PTEN was the direct target of miR-144 that was responsible for the alleviated effect of miR-144 inhibition on phenotypic switching of VSMCs. Notably, mice injected with miR-144 inhibitor attenuated the formation of neointimal lesions in response to wire injury and maintained the mature SMC marker expression inhibited the proliferation and migration of VSMCs. CONCLUSION: Our research exhibited that miR-144 knockdown attenuated intimal hyperplasia through inhibiting the VSMC phenotypic switching, which was partially mediated by directly targeting to PTEN. Taken together, these evidences suggested that miR-144 may act as a promising therapeutic target for arterial restenosis.