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Source: Biomaterials
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Total 77 results found since Jan 2013.

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

SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment.
In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs a...
Source: Biomaterials - May 2, 2014 Category: Materials Science Authors: Liu H, Li Y, Mozhi A, Zhang L, Liu Y, Xu X, Xing J, Liang X, Ma G, Yang J, Zhang X Tags: Biomaterials Source Type: research

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 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

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

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

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

Combinational delivery of c-myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy.
In this study, we developed a Lipid/Calcium/Phosphate (LCP) nanoparticle that combines chemotherapy with gene therapy. By encapsulating a chemodrug, gemcitabine monophosphate (GMP), and siRNA specific to the undruggable cMyc oncogene (cMyc siRNA) into a single nano-sized vesicle and systemically administering them to nude mice, we achieved potent anti-tumor activity in both subcutaneous and orthotopic models of NSCLC. The improvements in therapeutic response over either cMyc siRNA or GMP therapy alone, were demonstrated by the ability to effectively induce the apoptosis of tumor cells and the significant reduction of proli...
Source: Biomaterials - August 8, 2013 Category: Materials Science Authors: Zhang Y, Peng L, Mumper RJ, Huang L Tags: Biomaterials Source Type: research

In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models.
In this study, we report the use of siRNA/RGD gold nanoparticles capable of targeting tumor cells in a lung cancer syngeneic orthotopic murine model. Therapeutic RGD-nanoparticle treatment resulted in successful targeting evident from significant c-myc oncogene down-regulation followed by tumor growth inhibition and prolonged survival of lung tumor bearing mice, possibly via αvβ3 integrin interaction. Our results suggest that RGD gold nanoparticles-mediated delivery of siRNA by intratracheal instillation in mice leads to successful suppression of tumor cell proliferation and respective tumor size reduction. These results...
Source: Biomaterials - July 12, 2013 Category: Materials Science Authors: Conde J, Tian F, Hernández Y, Bao C, Cui D, Janssen KP, Ibarra MR, Baptista PV, Stoeger T, de la Fuente JM Tags: Biomaterials Source Type: research

Heat shock protein-mediated cell penetration and cytosolic delivery of macromolecules by a telomerase-derived peptide vaccine.
Abstract A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Here, we report an unexpected function of GV1001 as a cell-penetrating peptide (CPP). GV1001 was delivered into a variety of cells including various cancer cell lines and primary blood cells. Moreover, the delivered GV1001 was predominantly located in the cytoplasm of the cells, while a significantly higher proportion of TAT peptide was localized in the nucleus. Macromolecules such as proteins, DNA and siRNA, which were linked to GV1001 by direct covalent conjugation or n...
Source: Biomaterials - July 1, 2013 Category: Materials Science Authors: Lee SA, Kim BR, Kim BK, Kim DW, Shon WJ, Lee NR, Inn KS, Kim BJ Tags: Biomaterials Source Type: research

PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer.
In this study, we constructed a dual-modified liposome that incorporated PSA-responsive and PSMA-mediated liposomes and potentially offers double selectivity for PC. The folate moiety binds quickly to PSMA-positive tumors, and the PSA-responsive moiety is cleaved by PSA that was enriched in tumor tissues. The activated liposomes (folate and cell-penetrating peptides dual-modifications) are subsequently taken up by the tumor cells via polyarginine's penetrating effects and receptor-mediated endocytosis. To corroborate these assumptions, a series of experiments were conducted, including PSA-responsive peptide hydrolysis kine...
Source: Biomaterials - June 15, 2013 Category: Materials Science Authors: Xiang B, Dong DW, Shi NQ, Gao W, Yang ZZ, Cui Y, Cao DY, Qi XR Tags: Biomaterials Source Type: research

Trilayer micelles for combination delivery of rapamycin and siRNA targeting Y-box binding protein-1 (siYB-1).
In this study, it has been shown that PCL can encapsulate RAP with high loading efficiencies, and PAsp(DET) can successfully interact with siRNA for efficient transfection/knockdown with negligible cytotoxicity. The enhanced therapeutic efficacy of RAP/siYB-1 micelles was demonstrated in cell cultures and in a PC3 xenograft nude mouse model of human prostate cancer. Herein, we demonstrate that trilayer micelles are a promising approach to improve the simultaneous delivery of combination siRNA/drug therapies. PMID: 23768780 [PubMed - as supplied by publisher]
Source: Biomaterials - June 11, 2013 Category: Materials Science Authors: Zeng S, Xiong MP Tags: Biomaterials Source Type: research

A review of the current status of siRNA nanomedicines in the treatment of cancer.
Abstract RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes. This review aims to sum up the potential targets in numerous pathways and the properties of recently optimized siRNA synthetic nanomedicine...
Source: Biomaterials - May 30, 2013 Category: Materials Science Authors: Resnier P, Montier T, Mathieu V, Benoit JP, Passirani C Tags: Biomaterials Source Type: research