Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo.
ABSTRACT Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.
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ABSTRACT: In this work, we have prepared collagen-DNA complex on the surface of an electrode through electrostatic interaction and hydrogen bonding between collagen triple helix and DNA double helix. The prepared tubular material is then deposited on the electrode surface to form a film. Due to the excellent biocompatibility of collagen and DNA, the prepared biomaterial can provide a new platform for protein analysis. On the one hand, since collagen in the complex is the substrate of matrix metalloproteinases-2 (MMP-2), a new kind of electrochemical biosensor for the detection of MMP-2 can be developed. On the other, the collagen-DNA complex can be used to entrap proteins onto the electrode surface with the activity of the target proteins being well maintained, thus further analysis can be conducted on the target proteins.Electrochimica Acta 11/2013; 111:499-503. DOI:10.1016/j.electacta.2013.08.008 · 4.09 Impact Factor
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ABSTRACT: RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.PLoS ONE 03/2015; 10(3):e0116022. DOI:10.1371/journal.pone.0116022 · 3.53 Impact Factor
Chemical Reviews 04/2015; DOI:10.1021/cr5006793 · 45.66 Impact Factor