Polyion complex micelles composed of pegylated polyasparthydrazide derivatives for siRNA delivery to the brain

Huo, Hong; Gao, Yikun; Wang, Ying; Zhang, Jinghai; Wang, Zhan-you; Jiang, Tongying; Wang, Siling

doi:10.1016/j.jcis.2015.01.043

Cited by 41 publications

(20 citation statements)

References 26 publications

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“…6 There is a significant unmet need for simple, effective, and nontoxic siRNA delivery methods to modulate gene expression in primary neurons and brain. A range of approaches has been evaluated, 7 including AAV viruses, 8,9 peptide conjugates, 10 oligonucleotide formulations, 11 infusion of naked or slightly modified siRNAs, 12,13 ultrasound, 14 and convection-enhanced based delivery. 15 None of these approaches has received wide acceptance due to toxicity, a requirement for extensive repetitive dosing, and/or limited spatial distribution.…”

Section: Introductionmentioning

confidence: 99%

Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

Alterman

Hall

Coles

et al. 2015

Molecular Therapy - Nucleic Acids

132

187

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Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs) added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal toxicity. Thus, hsiRNAs embody a class of therapeutic oligonucleotides that enable simple and straightforward functional studies of genes involved in neuronal biology and neurodegenerative disorders in a native biological context.

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Section: Introductionmentioning

confidence: 99%

Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

Alterman

Hall

Coles

et al. 2015

Molecular Therapy - Nucleic Acids

132

187

View full text Add to dashboard Cite

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“…The incorporated metal complexes can contribute to the enhancement of the polymer hydrophobicity and crosslink the blocks; this leads to micelle core stabilization. The entrapment of hydrophilically charged molecules such as proteins and nucleic acids can be reached by the exploitation of electrostatic interactions and charge neutralization between the macromolecules and oppositely charged core‐forming blocks, such as polyethylenimine (PEI), PLys, or PAsp; this leads to the formation of core‐loaded polyion complex micelles . On the other hand, the solubilization and stabilization of a drug that can be otherwise damaged by a hydrolytic or proteolytic environment into a micelle core may protect the drug from such a hostile environment to some degree, in a manner analogous to drug encapsulation by semipermeable membranes.…”

Section: Polymeric Micelles As Drug Nanocarriersmentioning

confidence: 99%

Intelligent micellar polymeric nanocarriers for therapeutics and diagnosis

Topete

Barbosa

Taboada

2015

J of Applied Polymer Sci

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Polymeric micelles can be designed and synthesized to bear polymeric blocks with different hydrophilicities; this triggers their self-assembly into micellar aggregates similar to those generated with traditional surfactants. The basic structure consists of a hydrophobic core, capable of containing guest substances, and a hydrophilic shell, which stabilizes the payload and protects it from external degradation or prevents its quick elimination from the body. The accumulation of block copolymer micelles (BCMs) in a target cell or tissue can be accomplished by two main mechanisms, passive and active targeting; this allows the payload release at the site of action when desired. Hence, in this general overview, we pay special attention to newly developed single-stimulus-and multistimuli-responsive delivery systems capable of disassembling and reassembling (in some cases) as a response to changes in their physicochemical properties. Also, special interest is also devoted to multifunctional BCMs incorporating multiple therapeutic agents and/or multiple imaging contrast agents, which can be considered the new generation (third generation) of drug-delivery systems, that is, nanotheranostic platforms. Finally, a summary of BCM-based drug-delivery systems currently under clinical trials is given.

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“…Among all the interactions, the electrostatic reaction is an ideal option as it can deliver small and large charged molecules by reacting with block ionomers to form a stable core. 22,23 Usually, the PMs synthesized by electrostatic reactions consist of 2 oppositely charged polyelectrolytes. This electrostatic complex has a core-shell structure, which is termed as polyion complex micelle (PCM).…”

Section: Introductionmentioning

confidence: 99%

Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery

Wang

Huang

Shen

et al. 2017

IJN

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To achieve enhanced physical stability of poly(ethylene glycol)-poly( d , l -lactide) polymeric micelles (PEG-PDLLA PMs), a mixture of methoxy PEG-PDLLA-polyglutamate (mPEG-PDLLA-PLG) and mPEG-PDLLA-poly( l -lysine) (mPEG-PDLLA-PLL) copolymers was applied to self-assembled stable micelles with polyion-stabilized cores. Prior to micelle preparation, the synthetic copolymers were characterized by 1 H-nuclear magnetic resonance (NMR) and infrared spectroscopy (IR), and their molecular weights were calculated by 1 H-NMR and gel permeation chromatography (GPC). Dialysis was used to prepare PMs with deoxypodophyllotoxin (DPT). Transmission electron microscopy (TEM) images showed that DPT polyion complex micelles (DPT-PCMs) were spherical, with uniform distribution and particle sizes of 36.3±0.8 nm. In addition, compared with nonpeptide-modified DPT-PMs, the stability of DPT-PCMs was significantly improved under various temperatures. In the meantime, the pH sensitivity induced by charged peptides allowed them to have a stronger antitumor effect and a pH-triggered release profile. As a result, the dynamic characteristic of DPT-PCM was retained, and high biocompatibility of DPT-PCM was observed in an in vivo study. These results indicated that the interaction of anionic and cationic charged polyionic segments could be an effective strategy to control drug release and to improve the stability of polymer-based nanocarriers.

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Polyion complex micelles composed of pegylated polyasparthydrazide derivatives for siRNA delivery to the brain

Cited by 41 publications

References 26 publications

Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

Intelligent micellar polymeric nanocarriers for therapeutics and diagnosis

Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery

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