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Source: Biomacromolecules

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Total 92 results found since Jan 2013.

Surface modified HK:siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition.
Abstract We characterized in this study the pharmacokinetics and antitumor efficacy of histidine-lysine (HK):siRNA nanoplexes modified with PEG and a cyclic RGD (cRGD) ligand targeting αvβ3 and αvβ5 integrins. With non-invasive imaging, systemically administered surface modified HK:siRNA nanoplexes showed nearly 4-fold greater blood levels, 40% higher accumulation in tumor tissue, and 60% lower luciferase activity than unmodified HK:siRNA nanoplexes. We then determined whether the surface modified HK:siRNA nanoplex carrier was more effective in reducing MDA-MB-435 tumor growth with an siRNA targeting Raf-1. Re...
Source: Biomacromolecules - January 29, 2013 Category: Biochemistry Authors: Chou ST, Leng Q, Scaria P, Kahn JD, Tricoli LJ, Woodle M, Mixson AJ Tags: Biomacromolecules Source Type: research

Monodispersed Brush-like Conjugated Polyelectrolyte Nanoparticles with Efficient and Visualized SiRNA Delivery for Gene Silencing.
Abstract RNA interference is supposed to be one of the most powerful technologies for suppression of genes and treatment of diverse human diseases while the safely delivery and visualization of siRNA were still challenging. In this text, a novel type of monodispersed conjugated polymer nanoparticles PFNBr with brush-like molecular structure was introduced into siRNA delivery system. The nanoparticles in the delivery system simply and conveniently acquired dual functions which can not only carry high amount of siRNA to penetrate intracellularly for knockdown targeted mRNA but also act as signal agents for siRNA tra...
Source: Biomacromolecules - September 16, 2013 Category: Biochemistry Authors: Jiang R, Lu XM, Yang M, Deng W, Fan Q, Huang W Tags: Biomacromolecules Source Type: research

pH-Responsive Dynaplexes as Potent Apoptosis Inductors by Intracellular Delivery of Survivin siRNA
Biomacromolecules. 2023 Jul 31. doi: 10.1021/acs.biomac.3c00424. Online ahead of print.ABSTRACTGene knockdown by siRNA offers an unrestricted choice of targets and specificity based on the principle of complementary Watson-Crick base pairing with mRNA. However, the negative charge, large molecular size, and susceptibility to enzymatic degradation of siRNA impede its successful transfection, hence limiting its potential for therapeutic use. The development of efficient and safe siRNA transfection agents is, therefore, critical for siRNA-based therapy. Herein, we developed a protein-based biodynamic polymer (biodynamer) that...
Source: Biomacromolecules - July 31, 2023 Category: Biochemistry Authors: Yun Liu Salma Ashmawy Lorenz Latta Agnes-Valencia Weiss Alexander F Kiefer Sarah Nasr Brigitta Loretz Anna K H Hirsch Sangeun Lee Claus-Michael Lehr Source Type: research

A biodegradable stearylated peptide with internal disulfide bonds for efficient delivery of siRNA in vitro and in vivo.
In this study, a stearyl-peptide (SHR) was synthesized using arginine, histidine, cysteine and stearyl moiety. Further, the stearyl-peptides were cross linked by disulfide bonds to obtain cross-linked polypeptides (SHRss) with different molecular weight (SHRss1, SHRss2, SHRss3, SHRss4). The SHRss could effectively condense small interfering RNA (siRNA) into polyplexes with a hydrodynamic size of 100-300 nm and zeta potential of 20-40 mV. Flow cytometry and confocal laser scanning microscope studies revealed high cellular uptake and rapid dissociation behavior of SHRss2/siRNA complexes. Long-lasting high concentration of si...
Source: Biomacromolecules - February 16, 2015 Category: Biochemistry Authors: Tai Z, Wang X, Tian J, Gao Y, Zhang L, Yao C, Wu X, Zhang W, Zhu Q, Gao S Tags: Biomacromolecules Source Type: research

Development of Guanidinium-rich Protein Mimics for Efficient siRNA Delivery into Human T Cells.
Abstract RNA interference is gaining attention as a means to explore new molecular pathways and for its potential as a therapeutic; however, its application in immortal and primary T cells is limited due to challenges with efficient delivery in these cells types. Herein, we report the development of guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold that delivers siRNA into Jurkat T cells and human peripheral blood mononuclear cells (hPBMCs). Homopolymer and block copolymer PTDMs with varying numbers of guanidinium moieties were designed and teste...
Source: Biomacromolecules - August 31, 2015 Category: Biochemistry Authors: deRonde BM, Torres JA, Minter LM, Tew GN Tags: Biomacromolecules Source Type: research

Folate Receptor Targeted Delivery of siRNA and Paclitaxel to Ovarian Cancer Cells via Folate Conjugated Triblock Co-polymer to Overcome TLR4 Driven Chemotherapy Resistance.
This study demonstrates that PEI-g-PCL-b-PEG-Fol conjugates are a reliable delivery system for siRNA and are able to mediate therapeutic protein knockdown within ovarian cancer cells. Additionally, this study provides further evidence to link TLR4 levels to chemotherapy resistance. PMID: 26636884 [PubMed - as supplied by publisher]
Source: Biomacromolecules - December 4, 2015 Category: Biochemistry Authors: Jones SK, Lizzio V, Merkel O Tags: Biomacromolecules Source Type: research

Additive polyplexes to undertake siRNA therapy against CDC20 and survivin in breast cancer cells.
Abstract Small interfering RNA (siRNA) delivered to silence overexpressed genes associated with malignancies is a promising targeted therapy to decrease the uncontrolled growth of malignant cells. To create potent delivery agents for siRNA, here we formulated additive polyplexes of siRNA using linoleic acid-substituted polyethylenimine and additive polymers (hyaluronic acid, polyacrylic acid, dextran sulfate and methyl cellulose), and characterized their physicochemical properties and effectiveness. Incorporating polyanionic polymer along with anionic siRNA in polyplexes was found to decrease the ζ-potential of p...
Source: Biomacromolecules - September 17, 2018 Category: Biochemistry Authors: Parmar MB, K C RB, Löbenberg R, Uludag H Tags: Biomacromolecules Source Type: research

Comparison of Nanocomplexes with Branched and Linear Peptides for SiRNA Delivery.
Abstract Efficient delivery of siRNA remains the greatest technological barrier to the clinical implementation of RNA interference strategies. We are investigating the relationship between the biophysical properties of siRNA nanocomplexes and their transfection efficiency as an approach to the generation of improved formulations. Peptide based formulations are of great interest and so in this study we have compared nanocomplex formulations for siRNA delivery containing linear and branched oligolysine or oligoarginine peptides. Peptides were combined with cationic liposomes in siRNA formulations and compared for tr...
Source: Biomacromolecules - January 22, 2013 Category: Biochemistry Authors: Tagalakis AD, Saraiva L, McCarthy D, Gustafsson KT, Hart SL Tags: Biomacromolecules Source Type: research

RVG peptide-linked trimethylated chitosan for delivery of siRNA to the brain.
Abstract In this work, a peptide derived from the rabies virus glycoprotein (RVG) was linked to siRNA/trimethylated chitosan (TMC) complexes through bifunctional PEG for efficient brain-targeted delivery of siRNA. The physiochemical properties of the complexes, such as siRNA complexing ability, size and zeta potential, morphology, serum stability and cytotoxicity, were investigated prior to studying the cellular uptake, in vitro gene silencing efficiency and in vivo biodistribution. The RVG peptide-linked siRNA/TMC-PEG complexes showed increased serum stability, negligible cytotoxicity and higher cellular uptake t...
Source: Biomacromolecules - February 18, 2014 Category: Biochemistry Authors: Gao Y, Wang Z, Zhang J, Zhang Y, Huo H, Wang T, Jiang T, Wang S Tags: Biomacromolecules Source Type: research

Optimal Hydrophobicity in ROMP-based Protein Mimics Required for siRNA Internalization.
Abstract Exploring the role of polymer structure for the internalization of biologically relevant cargo, specifically siRNA, is of critical importance to the development of improved delivery reagents. Herein, we report guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold containing tunable hydrophobic moieties that promote siRNA internalization. Structure-activity relationships using Jurkat T cells and HeLa cells were explored to determine how the length of the hydrophobic block and the hydrophobic side chain compositions of these PTDMs impacted siR...
Source: Biomacromolecules - April 20, 2016 Category: Biochemistry Authors: deRonde BM, Posey ND, Otter R, Caffrey LM, Minter LM, Tew GN Tags: Biomacromolecules Source Type: research

Mapping Optimal Charge Density and Length of ROMP-based PTDMs for siRNA Internalization.
Abstract A fundamental understanding of how polymer structure impacts internalization and delivery abilities of biologically relevant cargoes, particularly siRNA, is of critical importance to the successful design of improved delivery reagents. Herein we report the use of ring-opening metathesis polymerization (ROMP) methods to synthesize two series of guanidinium-rich protein transduction domain mimics (PTDMs): one based on an imide scaffold that contains one guanidinium moiety per repeat unit and another based on a diester scaffold that contains two guanidinium moieties per repeat unit. By varying both the degre...
Source: Biomacromolecules - September 5, 2016 Category: Biochemistry Authors: Caffrey LM, deRonde BM, Minter LM, Tew GN Tags: Biomacromolecules Source Type: research

Pyruvate responsiveness based on α-oxohydrazone formation for intracellular siRNA release from polyion complex (PIC)-based carriers.
This study provides the rationale for a smart design of pyruvate-responsive materials in the cell, based on α-oxohydrazone formation. PMID: 31091092 [PubMed - as supplied by publisher]
Source: Biomacromolecules - May 14, 2019 Category: Biochemistry Authors: Takemoto H, Wang CL, Nomoto T, Matsui M, Tomoda K, Nishiyama N Tags: Biomacromolecules Source Type: research

Recent Advances of Polycationic siRNA Vectors for Cancer Therapy.
Abstract Small interfering RNAs (siRNAs) have recently emerged as a new class of biopharmaceuticals for the treatment of various diseases, including genetic diseases, viral infections, heritable disorders, and most prominently, cancer. However clinical applications of siRNA-based therapeutics through intravenous administration have been limited due to their rapid degradation and renal clearance, poor cellular uptake, low cytoplasmic release by escaping endocytic uptake and off-target effects. The success of siRNA-based therapeutics depends upon the design and creation of efficient delivery vectors that should be a...
Source: Biomacromolecules - June 21, 2020 Category: Biochemistry Authors: Bholakant R, Qian H, Zhang J, Huang X, Huang D, Feijen J, Zhong Y, Chen W Tags: Biomacromolecules Source Type: research

siRNA-Loaded Polyion Complex Micelle Decorated with Charge-Conversional Polymer Tuned to Undergo Stepwise Response to Intra-Tumoral and Intra-Endosomal pHs for Exerting Enhanced RNAi Efficacy.
This study aimed to develop an siRNA-loaded polyion complex (PIC) micelle equipped with a smart polymeric shell featuring tumor-targetability and endosome-escapability for enhanced RNAi activity in cancer cells. To this end, an acidic pH-responsive polypeptide was designed to exert a stepwise change in its charged state from negative to modestly positive and highly positive in response to slightly acidic environment of tumor (pH ~6.7) and further lowered-pH condition of late endosomal compartments (pH ~5.0), respectively, for selective binding to cancer cell surface and subsequent endosome disruption. This polypeptide, ter...
Source: Biomacromolecules - November 30, 2015 Category: Biochemistry Authors: Tangsangasaksri M, Takemoto H, Naito M, Maeda Y, Sueyoshi D, Kim HJ, Miura Y, Ahn J, Azuma R, Nishiyama N, Miyata K, Kataoka K Tags: Biomacromolecules Source Type: research