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Dual targeted delivery of statins and nucleic acids by chitosan-based nanoparticles for enhanced antiatherosclerotic efficacy
Biomaterials. 2021 Dec 15;280:121324. doi: 10.1016/j.biomaterials.2021.121324. Online ahead of print.ABSTRACTCardiovascular disease caused by atherosclerosis is a leading cause of morbidity and mortality worldwide. Owing to the synergistic regulation of cholesterol metabolism and lesion inflammation, the simultaneous administration of statins and nucleic acids is expected to alleviate atherosclerosis. In this work, we prepared atorvastatin- and galactose-modified trimethyl chitosan nanoparticles (GTANPs) with dual targeting to hepatocytes and lesional macrophages for encapsulating Baf60a siRNA (siBaf60a) and anti-miR-33 pD...
Source: Biomaterials - December 21, 2021 Category: Materials Science Authors: Ting Jiang Lu Xu Mengxin Zhao Fei Kong Xinrong Lu Cui Tang Chunhua Yin Source Type: research

Nanoparticle-based "Two-pronged" approach to regress atherosclerosis by simultaneous modulation of cholesterol influx and efflux.
Abstract Reduction of lipoprotein uptake by macrophages and stimulation of cholesterol efflux are two essential steps required for atherosclerotic plaque regression. We used the optimized mannose-functionalized dendrimeric nanoparticle (mDNP)-based platform for macrophage-specific delivery of therapeutics to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR ligand (LXR-L, to stimulate cholesterol efflux) - a novel "Two-pronged" approach to facilitate plaque regression. mDNP-mediated delivery of SR-A siRNA led to a significant reduction in SR-A expression with a corresponding decrease in uptake of ox...
Source: Biomaterials - August 14, 2020 Category: Materials Science Authors: He H, Wang J, Yannie PJ, Korzun WJ, Yang H, Ghosh S Tags: Biomaterials Source Type: research

Actively-targeted polyion complex micelles stabilized by cholesterol and disulfide cross-linking for systemic delivery of siRNA to solid tumors.
Abstract For small interfering RNA (siRNA)-based cancer therapies, we report an actively-targeted and stabilized polyion complex micelle designed to improve tumor accumulation and cancer cell uptake of siRNA following systemic administration. Improvement in micelle stability was achieved using two stabilization mechanisms; covalent disulfide cross-linking and non-covalent hydrophobic interactions. The polymer component was designed to provide disulfide cross-linking and cancer cell-targeting cyclic RGD peptide ligands, while cholesterol-modified siRNA (Chol-siRNA) provided additional hydrophobic stabilization to t...
Source: Biomaterials - June 12, 2014 Category: Materials Science Authors: Oe Y, Christie RJ, Naito M, Low SA, Fukushima S, Toh K, Miura Y, Matsumoto Y, Nishiyama N, Miyata K, Kataoka K Tags: Biomaterials Source Type: research

Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis.
We described here the mechanisms by which small interfering RNA (siRNA) molecules incorporated in reconstituted high density lipoprotein (rHDL) were efficiently transferred into the cytoplasm of cells to perform target-specific therapy of tumor angiogenesis. Using fluorescent-tagged apolipoprotein A-I (apoA-I) and cholesterol-conjugated siRNA (Chol-siRNA), it was confirmed with FACS and confocal microscopic measurements that Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes) were successfully established and apoA-I certainly was attached to the surface of Chol-siRNA-loaded lipoplexes (Lipos/Chol-siRNA complex...
Source: Biomaterials - May 27, 2014 Category: Materials Science Authors: Ding Y, Wang Y, Zhou J, Gu X, Wang W, Liu C, Bao X, Wang C, Li Y, Zhang Q Tags: Biomaterials Source Type: research

Tumor-specific delivery of siRNA using supramolecular assembly of hyaluronic acid nanoparticles and 2b RNA-binding protein/siRNA complexes.
Abstract Anticancer therapeutics delivering exogenous siRNA have been explored to suppress the tumor-associated genes, but several limitations of siRNA delivery such as tumor-targeted delivery, controlled siRNA release at the sites of interest, or instabilities of siRNA in physiological fluids should be preferentially addressed for its clinical applications. As an attempt to meet these criteria, we designed a supramolecular assembly, which was composed of cholesterol-bearing hyaluronic acid (HA-Chol) conjugates and 2b RNA-binding protein (2b)/siRNA complexes. In contrast to the traditional siRNA polyplexes using e...
Source: Biomaterials - May 19, 2014 Category: Materials Science Authors: Choi KM, Jang M, Kim JH, Ahn HJ Tags: Biomaterials Source Type: research

Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy.
In this study, low-density lipoprotein (LDL) was isolated from human plasma and loaded with cholesterol-conjugated siRNA to silence the multidrug resistant gene of tumors. Chol-siRNA/LDL-coupled N-succinyl chitosan nanoparticles loaded with doxorubicin (Dox-siRNA/LDL-SCS-NPs) were then prepared and characterised. The Dox-siRNA/LDL-SCS-NPs had average particle size of 206.4 ± 9.2 nm, entrapment efficiency of 71.06% ± 1.42%, and drug-loading amount of 12.35% ± 0.87%. In vitro antitumor activity revealed that cell growth was significantly inhibited. The accumulation of Dox by fluorescence microscopy and flow cytome...
Source: Biomaterials - April 24, 2014 Category: Materials Science Authors: Zhu QL, Zhou Y, Guan M, Zhou XF, Yang SD, Liu Y, Chen WL, Zhang CG, Yuan ZQ, Liu C, Zhu AJ, Zhang XN Tags: Biomaterials Source Type: research

Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA delivery.
In this study, the core-shell type lipid/rPAA-Chol hybrid nanoparticles (PEG-LP/siRNA NPs and T7-LP/siRNA NPs) were developed for improving in vivo siRNA delivery by modifying the surface of rPAA-Chol/siRNA nanoplex core with a lipid shell, followed by post-insertion of polyethylene glycol phospholipid (DSPE-PEG) and/or peptide (HAIYPRH, named as T7) modified DSPE-PEG-T7. The integrative hybrid nanostructures of LP/siRNA NPs were evidenced by dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), cryo-transmission electron microscope (Cryo-TEM) and surface plasmon resonance (SPR) assay. It was demonstr...
Source: Biomaterials - December 5, 2013 Category: Materials Science Authors: Gao LY, Liu XY, Chen CJ, Wang JC, Feng Q, Yu MZ, Ma XF, Pei XW, Niu YJ, Qiu C, Pang WH, Zhang Q Tags: Biomaterials Source Type: research

Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity.
In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into TM cells in vitro. NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of TM's) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into TM's. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of...
Source: Biomaterials - September 26, 2013 Category: Materials Science Authors: Hajdu P, Chimote AA, Thompson TH, Koo Y, Yun Y, Conforti L Tags: Biomaterials Source Type: research