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Source: Biomaterials

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Total 156 results found since Jan 2013.

Tumor-penetrating codelivery of siRNA and paclitaxel with ultrasound-responsive nanobubbles hetero-assembled from polymeric micelles and liposomes.
Abstract Drug resistance is a big problem in systemic chemotherapy of hepatocellular carcinoma (HCC), and nanomedicines loaded with both chemotherapeutic agents (e.g. paclitaxel, PTX) and siRNA's targeting antiapoptosis genes (e.g. BCL-2) possess the advantages to simultaneously overcome the efflux pump-mediated drug resistance and antiapoptosis-related drug resistance. However, tumor-penetrating drug delivery with this type of nanomedicines is extremely difficult due to their relatively big size compared to the single drug-loaded nanomedicines. Aiming at address this problem, US-responsive nanobubbles encapsulati...
Source: Biomaterials - April 17, 2014 Category: Materials Science Authors: Yin T, Wang P, Li J, Wang Y, Zheng B, Zheng R, Cheng D, Shuai X Tags: Biomaterials Source Type: research

The effect of combined IL10 siRNA and CpG ODN as pathogen-mimicking microparticles on Th1/Th2 cytokine balance in dendritic cells and protective immunity against B cell lymphoma.
Abstract Success of an immunotherapy for cancer often depends on the critical balance of T helper 1 (Th1) and T helper 2 (Th2) responses driven by antigen presenting cells, specifically dendritic cells (DCs). Th1-driven cytotoxic T cell (CTL) responses are key to eliminating tumor cells. It is well established that CpG oligonucleotides (ODN), a widely studied Toll-like receptor 9 (TLR9) agonist, used to enhance Th1 response, also induces high levels of the anti-inflammatory, Th2-promoting cytokine IL10, which could dampen the resulting Th1 response. Biomaterials-based immunomodulatory strategies that can reduce IL...
Source: Biomaterials - April 7, 2014 Category: Materials Science Authors: Pradhan P, Qin H, Leleux JA, Gwak D, Sakamaki I, Kwak LW, Roy K Tags: Biomaterials Source Type: research

The use of gene activated matrix to mediate effective SMAD2 gene silencing against hypertrophic scar.
Abstract Hypertrophic scar (HS) originates from the over-expression of transforming growth factor β (TGF-β) and downstream SMAD2. With attempts to rectify HS by RNA interference (RNAi) against SMAD2, we report the design of plasmid DNA encoding SMAD2 siRNA (pSUPER-SMAD2), and identify the optimal siRNA sequence toward maximal RNAi efficiency. To realize effective and sustained RNAi, we developed gene activated matrix (GAM) based on porous atelocollagen scaffold and embedded trimethyl chitosan-cysteine (TMCC)/pSUPER-SMAD2 polyplexes for promoting cell growth and gene transfection. The GAM exhibited porosity highe...
Source: Biomaterials - January 15, 2014 Category: Materials Science Authors: Yin L, Zhao X, Ji S, He C, Wang G, Tang C, Gu S, Yin C 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

The effect of RNAi silencing of p62 using an osmotic polysorbitol transporter on autophagy and tumorigenesis in lungs of K-ras(LA1) mice.
Abstract Treating cancer patients by conventional chemotherapy to achieve prolonged survival still remains complicated. Autophagy is a topic of considerable interest in recent times, as it may contribute greatly to tumor suppression. Recent studies indicate that autophagy-deficient cells accumulate high levels of p62, an ubiquitin-binding scaffold protein, involved greatly in tumorigenesis. Here, we synthesized an osmotically active polysorbitol-mediated transporter (PSMT) to downregulate p62 using an RNAi strategy and described the mechanism of how p62 silencing using PSMT/siRNA p62 system activates autophagy and...
Source: Biomaterials - November 21, 2013 Category: Materials Science Authors: Islam MA, Shin JY, Yun CH, Cho CS, Seo HW, Chae C, Cho MH Tags: Biomaterials Source Type: research

A review of ligand tethered surface engineered carbon nanotubes.
Abstract Carbon nanotubes (CNTs) have emerged as fascinating materials, exhibiting promising potential in receptor based targeting owing to their unique physicochemical properties (cell membrane penetration, high surface area and drug payload, biocompatibility, easy surface modification, photoluminescence property, and non-immunogenicity etc). The hydrophilicity, a major constrain associated with the first generation of CNTs i.e. pristine CNTs, could be overcome using functionalization techniques. In the last two decades variety of functionalized CNTs (f-CNTs) i.e. oxidized, amidated, acylated, surfactant and biop...
Source: Biomaterials - November 6, 2013 Category: Materials Science Authors: Mehra NK, Mishra V, Jain NK Tags: Biomaterials Source Type: research

Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds.
Abstract Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We anticipate that elucidation of the binding mechanism of HK with siRNA will provide greater insight into the self-assembly and delivery of the HK:siRNA polyplex. Non-covalent bonds between histidine residues and nucleic acids may enhance the stability of siRNA polyplexes. We first compared the polyplex biophysical properties of a branched HK with those of branched asparagine-lysine peptide (NK). Consistent with siRNA silencing experiments, gel electrophoresis demonstrated that the HK siRN...
Source: Biomaterials - October 22, 2013 Category: Materials Science Authors: Chou ST, Hom K, Zhang D, Leng Q, Tricoli LJ, Hustedt JM, Lee A, Shapiro MJ, Seog J, Kahn JD, Mixson AJ Tags: Biomaterials Source Type: research

Differential nanotoxicological and neuroinflammatory liabilities of non-viral vectors for RNA interference in the central nervous system.
Abstract Progression of RNA interference-based gene silencing technologies for the treatment of disorders of the central nervous system (CNS) depends on the availability of efficient non-toxic nanocarriers. Despite advances in the field of nanotechnology undesired and non-specific interactions with different brain-cell types occur and are poorly investigated. To this end, we studied the cytotoxic and neuroinflammatory effects of widely-used transfection reagents and modified amphiphilic β-cyclodextrins (CDs). All non-viral vectors formed positively charged nanoparticles with distinctive physicochemical properties...
Source: Biomaterials - October 16, 2013 Category: Materials Science Authors: Godinho BM, McCarthy DJ, Torres-Fuentes C, Beltrán CJ, McCarthy J, Quinlan A, Ogier JR, Darcy R, O'Driscoll CM, Cryan JF Tags: Biomaterials Source Type: research

Programmed nanoparticles for combined immunomodulation, antigen presentation and tracking of immunotherapeutic cells.
We report programmed nanoparticles (pNPs) that can tailor the immunotherapeutic function of primary bone marrow-derived dendritic cells (BMDCs) by ex vivo combined immunomodulation and track the in vivo migration of them after injection into body. Because DCs are the most effective antigen-presenting cells (APCs) that are able to present the antigens to T cells that contribute to tumor rejection, the maturation and monitoring of therapeutic DCs are essential for the efficient cancer immunotherapy. For combined immunomodulation of DCs, poly (lactic-co-glycolic acid) (PLGA) NPs containing both small interfering RNA (siRNA)...
Source: Biomaterials - October 11, 2013 Category: Materials Science Authors: Heo MB, Lim YT Tags: Biomaterials Source Type: research

The effect of serum in culture on RNAi efficacy through modulation of polyplexes size.
Abstract Serum in the culture medium is one crucial factor that compromises RNAi efficiency of non-viral vectors. However, mechanistic roles of serum in siRNA delivery remain unknown. In this work, we took one cationic polymer, pullulan chemically modified by spermine (termed as pullulan-spermine, Ps), as a siRNA carrier model to investigate the effects of serum on key steps in siRNA delivery including formation of Ps and siRNA polyplexes (Ps-siRNA), cellular uptake, lysosomal escape, and cytotoxicity. We demonstrate that low serum concentration (1.25% and 2.5%) in culture medium results in large particles of Ps-s...
Source: Biomaterials - October 10, 2013 Category: Materials Science Authors: Zhang W, Liu J, Tabata Y, Meng J, Xu H Tags: Biomaterials Source Type: research

Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells.
Abstract Nanoporous silicon particles (pSi), with a pore size in the range of 20-60 nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical ...
Source: Biomaterials - October 5, 2013 Category: Materials Science Authors: Zhang M, Xu R, Xia X, Yang Y, Gu J, Qin G, Liu X, Ferrari M, Shen H 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

Inhibition of hepatocellular carcinoma growth using immunoliposomes for co-delivery of adriamycin and ribonucleotide reductase M2 siRNA.
Abstract The chemotherapy combined with gene therapy has received great attention. We developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab' co-delivering adriamycin (ADR) and ribonucleotide reductase M2 (RRM2) siRNA (ADR-RRM2-TLPD), to achieve combined therapeutic effects in human hepatocellular carcinoma (HCC) overexpressing EGFR. The antitumor activity and mechanisms of ADR-RRM2-TLPD were investigated. The results showed that RRM2 expression was higher in HCC than in non-HCC tissue, and RRM2 siRNA inhibited HCC cell proliferation, suggesting th...
Source: Biomaterials - September 20, 2013 Category: Materials Science Authors: Gao J, Chen H, Yu Y, Song J, Song H, Su X, Li W, Tong X, Qian W, Wang H, Dai J, Guo Y Tags: Biomaterials Source Type: research

Acid-degradable core-shell nanoparticles for reversed tamoxifen-resistance in breast cancer by silencing manganese superoxide dismutase (MnSOD).
This study attempted to reverse tamoxifen (TAM)-resistance in breast cancer by silencing a mitochondrial enzyme, manganese superoxide dismutase (MnSOD), which dismutates TAM-induced reactive oxygen species (ROS) (i.e., superoxide) to less harmful hydrogen peroxide and hampers therapeutic effects. Breast cancer cells were co-treated with TAM and MnSOD siRNA-delivering nanoparticles (NPs) made of a siRNA/poly(amidoamine) (PAMAM) dendriplex core and an acid-degradable polyketal (PK) shell. The (siRNA/PAMAM)-PK NPs were designed for the PK shell to shield siRNA from nucleases, minimize detrimental aggregation in serum, and fac...
Source: Biomaterials - September 19, 2013 Category: Materials Science Authors: Cho SK, Pedram A, Levin ER, Kwon YJ Tags: Biomaterials Source Type: research

Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors.
In this study, we utilized human serum albumin (HSA), which is the most abundant of the plasma proteins, as a siRNA carrier for systemic tumor-targeted siRNA delivery. Both HSA and siRNA molecules were thiol-introduced to improve the binding affinity for each other. The resulting thiolated HSA (tHSA) and polymerized siRNA (psi) formed stable nanosized complexes (psi-tHSAs) by chemical crosslinking and self-crosslinking. After internalization, the psi-tHSAs showed target gene silencing activity in vitro comparable to conventional Lipofectamine™-siRNA complexes, without remarkable cytotoxicity. After intravenous injection...
Source: Biomaterials - September 16, 2013 Category: Materials Science Authors: Son S, Song S, Lee SJ, Min S, Kim SA, Yhee JY, Huh MS, Chan Kwon I, Jeong SY, Byun Y, Kim SH, Kim K Tags: Biomaterials Source Type: research