The use of small interfering RNAs (siRNAs) to down-regulate the expression of disease-associated proteins carries significant promise for the treatment of a variety of clinical disorders. One of the main barriers to the widespread clinical use of siRNAs, however, is their entrapment and degradation within the endolysosomal pathway of target cells. Here we report the trafficking and function of PP75, a non-toxic, biodegradable, lipid membrane disruptive anionic polymer composed of phenylalanine derivatized poly(L-lysine iso-phthalamide). PP75 is readily endocytosed by cells, safely permeabilizes endolysosomes in a pH dependent manner and facilitates the transfer of co-endocytosed materials directly into the cytoplasm. The covalent attachment of siRNAs to PP75 using disulfide linkages generates conjugates that effectively traffic siRNAs to the cytoplasm of target cells both in vitro and in vivo. In a subcutaneous malignant glioma tumor model, a locally delivered PP75-stathmin siRNA conjugate decreases stathmin expression in tumor cells and, in combination with the nitrosourea chemotherapy carmustine, is highly effective at inhibiting tumor growth. PP75 may be clinically useful for the local delivery of siRNAs, in particular for the treatment of solid tumors.
In this paper, we fabricated rutin-loaded silver nanoparticles (Rutin@AgNPs) as the nano-anticoagulant with antithrombotic function. The serum stability, anticoagulation activity, and bleeding risk of Rutin@AgNPs were evaluated. The results showed Rutin@AgNPs had good serum stability, hemocompatibility, and cytocompatibility. The anticoagulation activity of rutin was maintained, and its stability and aqueous solubility were improved. The Rutin@AgNPs could provide a sustained release to prolong the half-life of rutin. The results of the coagulation parameter assay and thrombus formation test in mice model showed that the activated partial thromboplastin time and prothrombin time were prolonged, and Rutin@AgNPs inhibited the thrombosis in the 48 h period. Moreover, the limited bleeding time indicated that the Rutin@AgNPs significantly minimized the hemorrhage risk of rutin. This Rutin@AgNPs is a potential anticoagulant for antithrombotic therapy.
The purpose of this study was to investigate the anti-Newcastle disease virus (NDV)
activities of baicalin from Scutellaria baicalensis, a Traditional
Chinese Medicine in vitro. Chicken embryo fibroblasts (CEFs) were
infected with NDV, and quantitative analysis of apoptotic cells was performed using flow
cytometry. Cytotoxicity and anti-viral activities of baicalin were studied using the MTT
method. The results showed that the maximal safe concentrations of baicalin to CEFs was 1
× 2−2 mg/ml. Baicalin could directly kill NDV, inhibit the
infectivity of NDV to CEF and block intracellular NDV. It inhibited the apoptosis of
NDV-infected CEFs and suppressed the spread of NDV. These results indicate that baicalin
has strong anti-NDV activity and has the potential for use as components of an antiviral
drug.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.