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Source: Nanomedicine : Nanotechnology, Biology, and Medicine
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Total 55 results found since Jan 2013.
Small molecule ligands for enhanced intracellular delivery of lipid nanoparticle formulations of siRNA
This study aimed to identify small molecules that enhance cellular uptake of LNP siRNA systems, then use them as LNP-associated ligands to improve gene silencing potency. Screening the Canadian Chemical Biology Network molecules for effects on LNP uptake into HeLa cells found that cardiac glycosides like ouabain and strophanthidin caused the highest uptake. Cardiac glycosides stimulate endocytosis on binding to plasma membrane Na+/K+ ATPase found in all mammalian cells, offering the potential to stimulate LNP uptake into various cell types. A PEG-lipid containing strophanthidin at the end of PEG (STR-PEG-lipid) was synthes...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - December 10, 2012 Category: Nanotechnology Authors: Yuen Yi C. Tam, Sam Chen, Josh Zaifman, Ying K. Tam, Paulo J.C. Lin, Steven Ansell, Michel Roberge, Marco A. Ciufolini, Pieter R. Cullis Tags: Pharmacology, Pharmaceutics, Drug Delivery, siRNA, Lipid NPs, Cardiac Glycosides Source Type: research
Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer
Abstract: The synergetic inhibitory effects on human pancreatic cancer by nanoparticle-mediated siRNA and arsenic therapy were investigated both in vitro and in vivo. Poly(ethylene glycol)-block-poly(l-lysine) were prepared to form siRNA-complexed polyplex and poly(ethylene glycol)-block-poly(dl-lactide) were prepared to form arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-in...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - September 11, 2013 Category: Nanotechnology Authors: Linjuan Zeng, Jingguo Li, Yong Wang, Chenchen Qian, Yinting Chen, Qiubo Zhang, Wei Wu, Zhong Lin, Jianzhong Liang, Xintao Shuai, Kaihong Huang Tags: Pathology, Neoplasms, PanC, Kras, [(siRNA)-PEG-PLL], [(Arsenic)-PEG-PDLL] Co-administration Source Type: research
Hybrid lipid–polymer nanoparticles for sustained siRNA delivery and gene silencing
Abstract: The development of controlled-release nanoparticle (NP) technologies has great potential to further improve the therapeutic efficacy of RNA interference (RNAi), by prolonging the release of small interfering RNA (siRNA) for sustained, long-term gene silencing. Herein, we present an NP platform with sustained siRNA-release properties, which can be self-assembled using biodegradable and biocompatible polymers and lipids. The hybrid lipid–polymer NPs showed excellent silencing efficacy, and the temporal release of siRNA from the NPs continued for over one month. When tested on luciferase-expressed HeLa cells and A...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - March 19, 2014 Category: Nanotechnology Authors: Jinjun Shi, Yingjie Xu, Xiaoyang Xu, Xi Zhu, Eric Pridgen, Jun Wu, Alexander R. Votruba, Archana Swami, Bruce R. Zetter, Omid C. Farokhzad Tags: Pharmacology, Nano-Enabled Drug Delivery, Controlled Release, Polymer-siRNA Hybrid Source Type: research
Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes
Abstract: Mechanistic understanding of intracellular trafficking is important for the development of small interfering RNA (siRNA) delivery vehicles. Here, we describe a novel methodology to quantitatively analyze nanocarrier-mediated disposition of siRNA. Cellular uptake and cytoplasmic release of siRNA over time were quantified by measuring the fluorescence intensities of fluorescently-labeled siRNAs and molecular beacons using flow cytometry. This method was used to investigate the cellular pharmacokinetics (PK) of siRNA delivery by SPANosomes (SP) and by cationic liposomes (CL). The results showed that the superior pha...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - October 31, 2012 Category: Nanotechnology Authors: Chenguang Zhou, Yue Zhang, Bo Yu, Mitch A. Phelps, L. James Lee, Robert J. Lee Tags: Pharmaceutics, siRNA Delivery, PKPD, Liposomes Source Type: research
High efficacy gold-KDEL peptide-siRNA nanoconstruct-mediated transfection in C2C12 myoblasts and myotubes
Abstract: Gold nanoparticles (AuNP) were conjugated with cysteine terminated KDEL (Lys-Asp-Glu-Leu) peptide and siRNA directed against NADPH Oxidase 4 (Nox4). Fluorescence microscopy analysis provided evidence of cytocellular retrograde transport pathways and sub-cellular colocalization of AuNP nanoconstructs in both undifferentiated C2C12 myoblasts and differentiated C2C12 myotubes. The cellular trafficking of AuNP nanoconstructs in undifferentiated myoblasts suggests stable and efficient transfection of siRNA as demonstrated by colocalization of AuNP-delivered KDEL and siRNA. The cellular uptake of AuNP nanoconstructs wa...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - August 8, 2013 Category: Nanotechnology Authors: Suresh Acharya, Rodney Allan Hill Tags: Cell Biology, Intracellular Transport Mechanism, Sirna-Au-KDEL Peptide Nanoconstructs Source Type: research
Preclinical development of siRNA therapeutics: Towards the match between fundamental science and engineered systems
Abstract: The evolution of synthetic RNAi faces the paradox of interfering with the human biological environment. Due to the fact that all cell physiological processes can be target candidates, silencing a precise biological pathway could be challenging if target selectivity is not properly addressed. Molecular biology has provided scientific tools to suppress some of the most critical issues in gene therapy, while setting the standards for siRNA clinical application. However, the protein down-regulation through the mRNA silencing is intimately related to the sequence-specific siRNA ability to interact accurately with the ...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - December 11, 2013 Category: Nanotechnology Authors: M. Videira, A. Arranja, D. Rafael, R. Gaspar Tags: Cell Biology and Genetics, Amino Acids, Nucleic Acids, siRNA Therapy, Basic Science vs. Engineering Source Type: research
Influence of cationic lipid composition on uptake and intracellular processing of lipid nanoparticle formulations of siRNA
This study reports on the in vivo gene silencing potency of lipid nanoparticle-siRNA systems containing ionizable cationic lipids. It is concluded that the superior potency of DLinKC2-DMA compared with DLinKDMA or DLinDMA can be attributed to their higher uptake thus improved ability to stimulate siRNA release from endosome.Graphical Abstract: Uptake of lipid nanoparticle (LNP) formulations of siRNA into cells. (1) LNP-siRNA associates with cell membrane followed by (2) internalization. As the pH decreases in the endosomes the ionizable cationic lipids associate with endogenous anionic lipids to destabilize the endosomal m...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - June 14, 2012 Category: Nanotechnology Authors: Paulo J.C. Lin, Yuen Yi C. Tam, Ismail Hafez, Ammen Sandhu, Sam Chen, Marco A. Ciufolini, Ivan R. Nabi, Pieter R. Cullis Tags: QV Pharmacology, Pharmaceutical Technology, Gene Transfection, Lipid NPs Source Type: research
Phospholipid-modified polyethylenimine-based nanopreparations for siRNA–mediated gene silencing: Implications for transfection and the role of lipid components
This study highlights the importance of amphiphile structure in promoting the interaction of PEI with cell membranes, siRNA uptake and intracellular delivery.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - August 8, 2013 Category: Nanotechnology Authors: Gemma Navarro, Sean Essex, Rupa R. Sawant, Swati Biswas, Dattatri Nagesha, Srinivas Sridhar, Conchita Tros de ILarduya, Vladimir P. Torchilin Tags: Pharmacology, siRNA, Gene Therapy Optimization, PEI-Graft-Phospholipid, GFP Source Type: research
Conformation-dependent binding and tumor-targeted delivery of siRNA by a designed TRBP2: Affibody fusion protein
Efficiency of systemically delivered siRNA in gene silencing is compromised due to lack of target-specific delivery and rapid clearance of siRNA by in vivo elimination pathways. We designed a fusion protein consisting of a dsRNA binding domain of Transactivation Response RNA Binding Protein (TRBP2) fused to ErbB2 binding affibody (AF) for target specific delivery of siRNA. Designated as TRAF, the fusion protein is stable and binds efficiently and specifically to siRNA, forming homogenous non-aggregated and nuclease-resistant particles that efficiently and selectively transport siRNA into HER-2 overexpressing cancer cells and tissues.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - February 23, 2015 Category: Nanotechnology Authors: Ghulam Hassan Dar, Vijaya Gopal, Madhusudhana Rao Source Type: research
Ultrasound-Responsive Microbubbles for Sonography-guided siRNA Delivery
RNA interfering is a gene therapeutic approach of great potential for cancer. However, tumor-targeted delivery of small interfering RNA (siRNA) solely based on the enhanced permeability and retention effect of nanocarriers is often insufficient. To address this challenge, siRNA encapsulated ultrasound-responsive microbubble (MB) was developed from polymeric siRNA micelles and liposomal MBs using hetero-assembling strategy. 1 MHz low-frequency ultrasound exposure of the tumor site after intratumoral injection of XIAP siRNA/MBs led to enhanced permeability of tumor tissues for much more siRNA delivery into deep tumor regions.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - December 27, 2015 Category: Nanotechnology Authors: Ping Wang, Tinghui Yin, Jingguo Li, Bowen Zheng, Xiaoli Wang, Yiru Wang, Jian Zheng, Rongqin Zheng, Xintao Shuai Source Type: research
Intracellular Trafficking and Exocytosis of a Multi-Component siRNA Nanocomplex
The objective of this study is to study post internalization trafficking of this siRNA nanocomplex and its multiple components like siRNA, protamine, and streptavidin, in HSCs. After internalization, the nanocomplex entrapped in early endosomes undergoes three possible routes including endosomal escape, exocytosis, and entrapment in lysosomes.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - March 9, 2016 Category: Nanotechnology Authors: Ravi S. Shukla, Akshay Jain, Zhen Zhao, Kun Cheng Source Type: research
Designing idiosyncratic hmPCL-siRNA nanoformulated capsules for silencing and cancer therapy
In this work, we have designed a siRNA-nanoformulation with mesoporous polycaprolactone (hmPCL) for silencing and cancer therapy. Average hollow core size of hmPCL nanocapsules used for nanoformulation is ~180nm with shell thickness of 10-20nm and mesopore size of ~5-10nm in diameter. Idiosyncratic capsules are biocompatible which has been confirmed with normal lymphocyte, K562 leukaemia cancer cells and on HepG2/EGFP cancer cells. In 1mg of hmPCL capsules up to 400ng of siRNA can be loaded. This nanoformulation enables to tune the dose dependent delivery up to ~93.25% (373ng) siRNA during therapy.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - November 7, 2015 Category: Nanotechnology Authors: Vijay Bhooshon Kumar, Himadri Medhi, Zhang Yong, Pradip Paik Source Type: research
An integrative approach for the large-scale identification of human genome kinases regulating cancer metastasis
Abstract: Kinases become one of important groups of drug targets. To identify more kinases being potential for cancer therapy, we developed an integrative approach for the large-scale screen of functional genes capable of regulating the main traits of cancer metastasis. We first employed self-assembled cell microarray to screen functional genes that regulate cancer cell migration using a human genome kinase siRNA library. We identified 81 genes capable of significantly regulating cancer cell migration. Following with invasion assays and bio-informatics analysis, we discovered that 16 genes with differentially expression in...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - June 10, 2013 Category: Nanotechnology Authors: Hanshuo Zhang, Po-Yen Wu, Ming Ma, Yanzhen Ye, Yang Hao, Junyu Yang, Shenyi Yin, Changhong Sun, John H. Phan, May D. Wang, Jianzhong Jeff Xi Tags: Pathology, Neoplasms, Metastasis, Human Kinases, siRNA Library Source Type: research
Rational modification of oligoarginine for highly efficient siRNA delivery: structure–activity relationship and mechanism of intracellular trafficking of siRNA
Recently, cell-penetrating peptides (CPPs) have received much attention for cellular delivery of therapeutic molecules. However, in the case of CPPs as carriers for siRNA delivery, their utility is often restricted by low cellular uptake and/or entrapment in endosomes. Here, in order to deliver siRNAs with high efficiency, oligoarginine, a prominent member in CPPs, is rationally modified with oligohistidine and stearyl moieties (STR-) by fully taking into account the formation of nanoparticles, uptake and intracellular trafficking.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - September 2, 2014 Category: Nanotechnology Authors: Dafeng Chu, Wen Xu, Ran Pan, Yong Ding, Weiping Sui, P. Chen Source Type: research
