Abstract:
:Synthetic small interfering RNA (siRNA) is a class of therapeutic entities that allow for specific silencing of target genes via RNA interference (RNAi) and comprise an enormous clinical potential for a variety of diseases, including cancer. However, efficient tissue-specific delivery of siRNA remains the major limitation in the development of RNAi-based cancer therapeutics. To achieve this, we have synthesized a series of sequence-defined oligomers, which include a cationic (oligoethanamino)amide core (for nanoparticle formation with siRNA), cysteines (as bioreversible disulfide units), and a polyethylene glycol chain (for shielding of surface charges) coupled to a terminal targeting ligand. The antifolate drug methotrexate (MTX), a well-established chemotherapeutic agent, serves as both targeting ligand and anticancer agent. The oligomers form homogeneous spherical siRNA polyplexes with a hydrodynamic diameter of approximately 6 nm. These polyplexes access KB cells by binding to the folate receptor in a MTX-dependent manner and induce efficient gene silencing activity in vitro. Impressively, in the in vivo studies, MTX-conjugated polyplexes significantly increase the intratumoral retention (168 h) of the siRNA, as compared to alanine-substituted non-targeted control polyplexes (48 h). The combination of MTX-conjugated polyplexes and eglin 5 (EG5) siRNA provides enhanced antitumoral potency with 50% of recurrence-free survival of KB tumor-bearing mice. The design of such siRNA carrier systems with a dual-functional ligand for cellular delivery and augmented tumor suppression could be a valuable strategy for translating RNAi-based cancer therapeutics to the clinics.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Lee DJ,Kessel E,Edinger D,He D,Klein PM,Voith von Voithenberg L,Lamb DC,Lächelt U,Lehto T,Wagner Edoi
10.1016/j.biomaterials.2015.11.004subject
Has Abstractpub_date
2016-01-01 00:00:00pages
98-110eissn
0142-9612issn
1878-5905pii
S0142-9612(15)00894-7journal_volume
77pub_type
杂志文章相关文献
BIOMATERIALS文献大全abstract::The in vivo properties of a new kind of calcium phosphate cement were investigated in this study. Calcium phosphate cement was implanted as paste into femoral bone and dorsal muscle of dogs for 3 and 6 months, and as prehardened form into thigh muscles of dogs for 1, 2 and 6 months. Histology was performed on thin un-...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(00)00016-8
更新日期:2000-06-01 00:00:00
abstract::This paper presents for the first time a mathematical model for a mechanism of controlled drug release involving both ion exchange and transient counter diffusion of a drug and counterions. Numerical analysis was conducted to study the effect of different factors on drug release kinetics including environmental condit...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2007.11.044
更新日期:2008-04-01 00:00:00
abstract::A series of mesoporous silica nanoparticles (MSNs) were synthesized using the co-structure directing method. A non-cytotoxic anionic surfactant, undec-1-en-11-yltetra(ethylene glycol) phosphate monoester surfactant (PMES), was used as a structure directing agent (SDA) together with aminopropyltrimethoxysilane that fun...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2011.04.077
更新日期:2011-09-01 00:00:00
abstract::A homogeneous glycidyl acrylate polymer (GAP) has been grafted on to polytetrafluoroethylene (PTFE) and polyethylene (PE) using a modified plasma glow discharge technique with glycidyl acrylate. The polymeric layer appears to be extremely stable to acidic media and to common organic solvents. The modified surface can ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(90)90083-3
更新日期:1990-10-01 00:00:00
abstract::Nanocarriers possess advanced physicochemical properties that improve bioavailability, enhance cellular dynamics, and control targetability in drug delivery. In particular, dendritic polyglycerol is a promising new biocompatible scaffold for drug delivery. The present explores the structure-biocompatibility relationsh...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2010.02.001
更新日期:2010-05-01 00:00:00
abstract::Mesenchymal condensation is a pre-requisite of chondrogenesis during embryonic development. The current understanding of chondrogenesis is limited in terms of chondrogenic condensation mechanisms. In particular, the role of matrix stiffness on homotypic cell-cell interactions leading to the establishment of distinct a...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2009.08.019
更新日期:2009-11-01 00:00:00
abstract::Skeletal muscle tissue engineering represents an attractive approach to overcome problems associated with autologous transfer of muscle tissue and provides a valid alternative in muscle regeneration enhancement. The aim of this study was to investigate the suitability, as scaffold for skeletal muscle tissue engineerin...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2004.11.035
更新日期:2005-08-01 00:00:00
abstract::Micropipette aspiration (MA) has been used extensively in biomechanical investigations of un-adhered cells suspended in media. In the current study, a custom MA system is developed to aspirate substrate adhered spread cells. Additionally, the system facilitates immuno-fluorescent staining of aspirated cells to investi...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2014.01.056
更新日期:2014-04-01 00:00:00
abstract::Different families of functionalized polymers with potential as biomaterials, or for biomaterial modification, have been investigated. In particular, degradation studies have been performed on poly(amidoamines), a family of polymers obtained by polyaddition of amines to bisacrylamides, and endowed with heparin-complex...
journal_title:Biomaterials
pub_type: 杂志文章,评审
doi:10.1016/0142-9612(94)90275-5
更新日期:1994-12-01 00:00:00
abstract::We report a reducible copolymer self-assembled with superparamagnetic iron oxide nanoparticles (SPIONs) to deliver doxorubicin (DOX) for cancer therapy. The copolymer of reducible polyamidoamine (rPAA) with poly(ethylene glycol)(PEG)/dodecyl amine graft was synthesized by Michael addition. rPAA@SPIONs were formed by t...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.10.057
更新日期:2014-01-01 00:00:00
abstract::We show here, that the proapoptotic peptide, KLAKLAKKLAKLAK (KLA), which by itself does not penetrate cell membranes, can do so when fused to a protein transduction domain derived from NH(2)-terminus of translationally controlled tumor protein (TCTP-PTD, MIIYRDLISH). Once inside the cell, the conjugated KLA exerts its...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2011.03.074
更新日期:2011-08-01 00:00:00
abstract::Various compositions of Na2OCaO-P2O5 glasses are prepared to estimate glass formation, dissolution properties and cytotoxicity. In the wide composition range of 40 mol% of P2O5 or more, clear glass samples were obtained. The estimated glass forming region was consistent with other ternary phosphate glass systems. The ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(98)00136-7
更新日期:1998-12-01 00:00:00
abstract::The present in vitro study investigates the cellular interaction of primary human osteoblasts with human and bovine solvent dehydrated cancellous bone (SDCB) discs. These are bio-implants from solvent dehydrated, gamma-irradiated preserved human and bovine cancellous bone, pre-treated to remove all cells, genetic comp...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(03)00205-9
更新日期:2003-09-01 00:00:00
abstract::Although dendritic nanoparticles have been prepared by many different methods, control over their degree of branching (DB) is still impossible, preventing us from understanding the effect of the DB on the properties of the nanodendrites as cancer therapeutics. Herein, we developed a novel seed-mediated method to prepa...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2016.06.033
更新日期:2016-10-01 00:00:00
abstract::A quantitative comparison between nuclear DNA release from carriers and their transfection activity would be highly useful for improving the effectiveness of non-viral gene vectors. We previously reported that, for condensed DNA particles, a close relationship exists between the efficiency of DNA release and transfect...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2012.01.049
更新日期:2012-05-01 00:00:00
abstract::A method to fabricate porous, biodegradable conduits using a combined injection molding, thermally induced phase transition technique was developed which produced conduits with dimensionally toleranced, longitudinally aligned channels. The geometry of the channels was designed to approximate the architecture of periph...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(02)00409-x
更新日期:2003-02-01 00:00:00
abstract::To investigate the role that the micro/nano-environment plays on the differentiation pathway of bone marrow stromal cells (BMSCs) into osteoblasts, we employed a 2D substrate coated with turnip yellow mosaic virus (TYMV) particles. TYMV is a non-enveloped icosahedral plant virus which has an average diameter 28 nm and...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2008.06.029
更新日期:2008-10-01 00:00:00
abstract::Polymethyl methacrylate (PMMA) films were treated by oxygen plasma discharge followed by acrylic acid (AA) grafting. The amount of carboxyl groups introduced by the grafting of AA on to the film surfaces was in the range 0.47-9.48 mumol/cm2, depending on the pressure of the plasma chamber during the discharge treatmen...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(93)90045-4
更新日期:1993-08-01 00:00:00
abstract::Metastasis of cancer makes up the vast majority of cancer-related deaths, and it usually initiates from tumor cells invasiveness and develops through tumor neovasculature. In this work, we have fabricated a CD44/neuropilin dual receptor-targeting nanoparticulate system (tLyP-1-HT NPs) with endogenous or FDA approved c...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2017.05.022
更新日期:2017-08-01 00:00:00
abstract::Irradiated, thermally stabilized, highly cross-linked UHMWPE bearings have demonstrated superior wear performance and improved in vitro oxidation resistance compared with terminally gamma-sterilized bearings, yet retrieval analysis reveals unanticipated in vivo oxidation in these materials despite fewer or no measurab...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2014.02.019
更新日期:2014-05-01 00:00:00
abstract::Chitosan-based nanofibers with an average fiber diameter controllable from a few microns down to approximately 40 nm and a narrow size distribution were fabricated by electrospinning solutions containing chitosan, polyethylene oxide (PEO), and Triton X-100. Rheological study showed a strong dependence of spinnability ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2005.03.027
更新日期:2005-11-01 00:00:00
abstract::Construction of biodegradable, three-dimensional scaffolds for tissue engineering has been previously described using a variety of molding and rapid prototyping techniques. In this study, we report and compare two methods for fabricating poly(DL-lactide-co-glycolide) (PLGA) scaffolds with feature sizes of approximatel...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(03)00052-8
更新日期:2003-06-01 00:00:00
abstract::Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2017.11.006
更新日期:2018-02-01 00:00:00
abstract::In this paper, we describe interactions between neural cells and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) toward development of electrically conductive biomaterials intended for direct, functional contact with electrically active tissues such as the nervous system, heart, and skeletal muscle. We...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2006.11.026
更新日期:2007-03-01 00:00:00
abstract::Natural materials exhibit anisotropy with variations in soluble factors, cell distribution, and matrix properties. The ability to recreate the heterogeneity of the natural materials is a major challenge for investigating cell-material interactions and for developing biomimetic materials. Here we present a generic flui...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2009.12.012
更新日期:2010-03-01 00:00:00
abstract::Duchenne Muscular Dystrophy (DMD) is a fatal genetic disorder currently having no cure. Here we report that culture substrates patterned with nanogrooves and functionalized with Matrigel (or laminin) present an engineered cell microenvironment to allow myotubes derived from non-diseased, less-affected DMD, and severel...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2018.08.047
更新日期:2018-11-01 00:00:00
abstract::There are few suitable techniques available to sterilize biodegradable polyester three-dimensional tissue engineering scaffolds because they are susceptible to degradation and/or morphological degeneration by high temperature and pressure. We used a novel polyllactide-co-glycolide) scaffold (Osteofoam) to determine th...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(00)00136-8
更新日期:2001-01-01 00:00:00
abstract::Driven by the clinical need for a strong tissue adhesive with elastomeric material properties, a departure from legacy crosslinking chemistries was sought as a multipurpose platform for tissue mending. A fresh approach to bonding wet substrates has yielded a synthetic biomaterial that overcomes the drawbacks of free-r...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2020.120215
更新日期:2020-11-01 00:00:00
abstract::Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control w...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2015.11.023
更新日期:2016-03-01 00:00:00
abstract::Endothelial cells derived from the bovine pulmonary artery (line CPAE, CCL 209, American Tissue Culture Collection, Rockville, MD, USA) were cultured on pristine or fluorine ion-irradiated polystyrene (5 x 10(12) or 5 x 10(14) F ions/cm2, 150 keV). At 24-h post-seeding interval, the number of cells which adhered to th...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(00)00009-0
更新日期:2000-06-01 00:00:00