Thrombotic diseases have a high rate of mortality and disability, and pose a serious threat to global public health. Currently, most thrombolytic drugs especially protein drugs have a short blood‐circulation time, resulting in low thrombolytic efficiency. Therefore, a platelet membrane (Pm) cloaked nanotube (NT‐RGD/Pm) biomimetic delivery system with enhanced thrombolytic efficiency is designed. Nanotubes (NT) with an excellent clot‐penetration properties are used to load a protein thrombolytic drug urokinase (Uk). Platelet‐targeting arginine glycine‐aspartic peptide (RGD) is grafted onto the surface of the nanotubes (NT‐RGD) prior to cloaking. Multiple particle tracking (MPT) technique and confocal laser scanning microscope (CLSM) analysis are applied and the results show that the nanotubes possess a strong penetration and diffusion capacity in thrombus clots. After the Pm cloaking on NT‐RGD/Uk, it shows a thrombus microenvironmental responsive release property and the half‐life of Uk is six times longer than that of free Uk. Most importantly, NT‐RGD‐Uk/Pm exhibits a 60% thrombolytic efficiency in the FeCl3‐induced thrombosis mouse model, and it is able to significantly reduce the bleeding side effects of Uk. This Pm‐cloaked nanotube system is an effective and promising platform for the controlled and targeted delivery of drugs for the thrombus treatment.
In article number 2205260, Fazheng Ren, Yuan Li, and co-workers developed natureinspired platelet membrane-cloaked nanotubes conjugated with targeting arginine glycineaspartic peptide and thrombolytic agent urokinase to achieve clot-targeting and penetrating. This biomimetic carrier showed a promising effect in improving the thrombolytic efficiency in vitro and in vivo.
The research was implemented to assess the safety of feeding excess of pyrroloquinoline quinone disodium (PQQ·Na2) to 108 Duroc × Landrace × Large White weaned pigs (BW = 8.38 ± 0.47 kg). Pigs were weaned at 28 d and randomly distributed to one of three diets with six replicates and six pigs per replicate (three males and three females). Pigs in the control group were fed a corn-soybean meal-based diet (without growth promoter) while the two experimental diets were supplied with 7.5 and 75.0 mg/kg PQQ·Na2, respectively. Average daily gain (ADG), average daily feed intake (ADFI), feed conversion (F:G), diarrhea incidence, hematology, serum biochemistry, organ index and general health were determined. Diets supplementation with 7.5 mg/kg PQQ·Na2 in weaned pigs could increase ADG during the entire experimental period (p < 0.05). And there was a tendency to decrease F:G (p = 0.063). The F:G of weaned pigs fed 7.5 and 75.0 mg/kg PQQ·Na2 supplemented diets was decreased by 9.83% and 8.67%, respectively, compared to the control group. Moreover, pigs had reduced diarrhea incidence (p < 0.01) when supplemented with PQQ·Na2. No differences were observed between pigs supplemented with 0.0, 7.5 and 75.0 mg/kg PQQ·Na2 diets on hematological and serum biochemical parameters as well as histological assessment of heart, liver, spleen, lung and kidney. At day 14, pigs had increased activity of glutathione peroxidase (GSH-Px) (p < 0.05), catalase (CAT) (p < 0.05) and total antioxidant capacity (T-AOC) (p < 0.05), and the serum concentration of malondialdehyde (MDA) was decreased (p < 0.01) with PQQ·Na2 supplementation. At day 28, pigs had increased activities of total superoxide dismutase (T-SOD) (p < 0.01), GSH-Px (p < 0.01), CAT (p < 0.05) and T-AOC (p < 0.01), and serum concentration of MDA was lower (p < 0.01) with PQQ·Na2 supplementation. In conclusion, PQQ·Na2 can improve weaned pigs growth performance and serum antioxidant status. Meanwhile high PQQ·Na2 inclusion of 75.0 mg/kg does not appear to result in harmful effects on growth performance of pigs.
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