排序方式: 共有193条查询结果,搜索用时 31 毫秒
141.
Anna Avi?ó Sandra M. Ocampo Clara Caminal José Carlos Perales Ramon Eritja 《Molecular diversity》2009,13(3):287-293
Oligoribonucleotide conjugates carrying nuclear localization peptide sequences at the 3′-end were prepared stepwise on a single
support. The siRNA duplex carrying the nuclear localization peptide sequence at the 3′-end of the passenger strand has similar
inhibitory properties as those of unmodified or cholesterol-modified RNA duplexes. 相似文献
142.
Koen Raemdonck Tinneke G. Van Thienen Roosmarijn E. Vandenbroucke Niek N. Sanders Joseph Demeester Stefaan C. De Smedt 《Advanced functional materials》2008,18(7):993-1001
To apply siRNA as a therapeutic agent, appropriate attention should be paid to the optimization of the siRNA gene silencing effect, both in terms of magnitude and duration. Intracellular time‐controlled siRNA delivery could aid in tailoring the kinetics of siRNA gene knockdown. However, materials with easily tunable siRNA release properties have not been subjected to thorough investigation thus far. This report describes cationic biodegradable dextran microgels which can be loaded with siRNA posterior to gel formation. Even though the siRNAs are incorporated in the hydrogel network based on electrostatic interaction, still a time‐controlled release can be achieved by varying the initial network density of the microgels. To demonstrate the biological functionality of the siRNA loaded gels, we studied their cellular internalization and enhanced green fluorescent protein (EGFP) gene silencing potential in HUH7 human hepatoma cells. 相似文献
143.
Seung‐Woo Cho Michael Goldberg Sun Mi Son Qiaobing Xu Fan Yang Ying Mei Said Bogatyrev Robert Langer Daniel G. Anderson 《Advanced functional materials》2009,19(19):3112-3118
Here, nanoparticles composed of lipid‐like materials (lipidoids) to facilitate non‐viral delivery of small interfering RNA (siRNA) to endothelial cells (ECs) are developed. Nanoparticles composed of siRNA and lipidoids with small size (~200 nm) and positive charge (~34 mV) are formed by self‐assembly of lipidoids and siRNA. Ten lipidoids are synthesized and screened for their ability to facilitate the delivery of siRNA into ECs. Particles composed of leading lipidoids show significantly better delivery to ECs than a leading commercially available transfection reagent, Lipofectamine 2000. As a model of potential therapeutic application, nanoparticles composed of the top performing lipidoid, NA114, are studied for their ability to deliver siRNA targeting anti‐angiogenic factor (SHP‐1) to human ECs. Silencing of SHP‐1 expression significantly enhances EC proliferation and decreases EC apoptosis under a simulated ischemic condition. 相似文献
144.
GUAN Shuwen YU Xiaoxuan LI Junyang XU Heng HAN Wenzhao SHI Guannan XU Jia WANG Liping 《高等学校化学研究》2019,35(3):434-439
Small interfering RNA(siRNA) has been proved to be a powerful tool for silencing target gene in cells, raising the possibility that siRNA can be employed as a therapy for treating cancers and other genetic diseases. However, siRNA transfection has the limitation due to the difficulty in the delivery of siRNA to target cells and tissues. To explore an efficient biocompatible siRNA delivery system, cationic diphenylalanine vesicles(CDPVs) were constructed to transfer survivin siRNA to human ovarian cancer cells. The morphology of CDPVs was characterized by scanning electron microscopy(SEM) and the distribution of survivin siRNA was characterized by confocal laser scanning microscopy, which reveal that diphenylalanine and the survivin siRNA were successfully co-delivered. After co-incubation for 48 h, the CDPVs/siRNA exhibited enhanced tumor cell growth inhabitation and apoptosis inducted in human SK-OV-3 ovarian carcinoma cells. Overall, CDPVs is an efficient siRNA delivery system and has a promising prospect for cancer therapy. 相似文献
145.
Nadine Leber Leonard Kaps Aiting Yang Misbah Aslam Mariacristina Giardino Adrian Klefenz Niklas Choteschovsky Sebastian Rosigkeit Asmaa Mostafa Lutz Nuhn Detlef Schuppan Rudolf Zentel 《Macromolecular bioscience》2019,19(7)
Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re‐polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA‐loaded cationic nanogels are reported with α‐mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α‐mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determined by dynamic light scattering and cryogenic electron transmission microscopy. α‐Mannosyl surface modification is confirmed by agglutination with concanavalin A. SiRNA‐loaded ManNP preferentially targets the overexpressed mannose receptor CD206 on M2 macrophages, as shown by in vitro cell uptake studies in M2 polarized primary macrophages. This specificity is confirmed, since ManNP uptake could be reduced by blocking of CD206 with mannan. Effective ManNP‐guided siRNA delivery is confirmed by sequence‐specific gene knockdown of CSF‐1R in M2‐type macrophages exclusively, while the expression levels in M1‐polarized macrophages is not affected. In conclusion, α‐mannosyl‐functionalized ManNPs are promising universal siRNA carriers for targeted immunomodulatory treatment of immunosuppressive macrophages. 相似文献
146.
siRNA Delivery: A Fluorinated Bola‐Amphiphilic Dendrimer for On‐Demand Delivery of siRNA,via Specific Response to Reactive Oxygen Species (Adv. Funct. Mater. 47/2016)
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147.
A Multi‐RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs
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148.
Chip‐Free Microscale‐Incubator‐Based Synthesis of Chitosan‐Based Gene Silencing Nanoparticles
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Noemi Gaglianone Michael Lykke Hvam Hüsnü Aslan Mingdong Dong Kenneth A. Howard Yi‐Ping Ho 《Particle & Particle Systems Characterization》2016,33(5):279-285
The development of polymer‐based nanoparticles to ferry siRNA continues to evolve. It is becoming increasingly apparent that gene silencing nanoparticles produced by conventional bulk manufacturing techniques often exhibit physicochemical heterogeneity within and between batches that can affect the biological performance. Here a new facile and robust “chip‐free” method is presented, termed chip‐free agitation‐generated droplets (CAD) preparation, using chitosan‐based gene silencing nanoparticles as an example. The CAD‐prepared silencing particles, in comparison to the particles prepared by the conventional bulk protocol, exhibit lower surface charge (9 mV vs 21 mV at N/P = 5), higher stability (≈40% higher binding affinity and up to 30% less morphological deformation), and are less prone to aggregation measured by nanoparticle tracking analysis over a period of one month. Furthermore, these physical attributes contribute up to 19% higher in cell viability at N/P = 5, while the gene silencing of enhanced green fluorescent protein remains constant in a human cell line. Control of particle properties is necessary to advance siRNA‐based delivery; the CAD preparation represents a physical complement to chemical design modifications, which can be readily transferred among research labs and utilized for alternative polymer systems. 相似文献
149.
Jiandong Yang Shanzhou Duan Huan Ye Chenglong Ge Chunxian Piao Yongbing Chen Minhyung Lee Lichen Yin 《Advanced functional materials》2021,31(21):2008960
Pulmonary delivery of anti-inflammatory siRNA holds great potential in mitigating the cytokine storm during severe pneumonia. However, commonly utilized polycationic siRNA delivery vehicles can hardly penetrate the mucus barrier, thus greatly hurdling their therapeutic efficacy. Herein, TNF-α siRNA (siTNF-α) delivery nanocomplexes (NCs) are engineered with mucus/cytomembrane dual-penetration capabilities, realized via surface-coating of NCs with RC, an inflammation-sheddable, charge-reversal pro-peptide of RAGE-binding peptide (RBP). RC-coated dendritic poly-L-lysine/siTNF-α (DsT) NCs possess negative surface charges, and can thus efficiently penetrate the mucus layer after intratracheal administration. In the inflamed alveolar space with mild acidity, RC recovers to the cationic RBP and shed off, re-exposing the DsT NCs that efficiently transfect the alveolar macrophages and provokes TNF-α silencing. Thus, siTNF-α and RBP cooperatively alleviate the uncontrolled inflammation during acute lung injury. This study renders a unique approach for mediating trans-mucus nucleic acid delivery, and will find promising utilities for the treatment of severe pneumonia. 相似文献
150.
Johan Karlsson Stephany Y. Tzeng Shayan Hemmati Kathryn M. Luly Olivia Choi Yuan Rui David R. Wilson Kristen L. Kozielski Alfredo Quiñones-Hinojosa Jordan J. Green 《Advanced functional materials》2021,31(17):2009768
Clinical translation of polymer-based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA-mediated knockdown in both glioma and melanoma cells in high-serum conditions compared to non-crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue-mediated siRNA delivery beyond the liver, unlike conventional nanoparticle-based delivery. These attributes of XbNPs facilitate robust siRNA-mediated knockdown in vivo in melanoma tumors colonized in the lungs following systemic administration. Thus, biodegradable polymeric nanoparticles, via photocrosslinking, demonstrate extended colloidal stability and efficient delivery of RNA therapeutics under physiological conditions, and thereby potentially advance systemic delivery technologies for nucleic acid-based therapeutics. 相似文献