Effects of hydrophobic core components in amphiphilic PDMAEMA nanoparticles on siRNA delivery

Han, Shangcong; Cheng, Qiang; Wu, Yidi; Zhou, Jinyun; Long, Xingwen; Wei, Tuo; Huang, Yuanyu; Zheng, Shuquan; Zhang, Jianhua; Deng, Liandong; Wang, Xiaoxia; Liang, Xing‐Jie; H, Cao; Liang, Zicai; Dong, Anjie

doi:10.1016/j.biomaterials.2015.01.026

Cited by 63 publications

(56 citation statements)

References 51 publications

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“…Considering that the Gu + /PO 3 4− salt bridge consists of electrostatic and hydrogen bond interactions, salt‐bridged siRNA nanomedicines can be expected to show better stability in blood than nanomedicines with single electrostatic interaction (NH 3 + /PO 3 4− ) as commonly seen with amine bearing polymers. In addition, hydrophobic interactions are broadly reported to increase the stability of siRNA nanomedicines . Thus, we hypothesized that if we incorporated both the Gu + /PO 4− salt bridge and a hydrophobic interaction in the formulation of polymeric siRNA nanomedicines, the resultant “triple‐interaction”‐stabilized siRNA nanomedicines could be expected to demonstrate superior stability.…”

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confidence: 99%

ROS‐Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy

et al. 2019

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Most brain diseases including brain tumor and dementia are fatal without current therapeutic solutions. [1] Small interfering RNA (siRNA) technology has demonstrated inherent advantages and significant potential for treating numerous tumor types, [2] owing to its high specificity, low dose requirement and relatively simple drug development process. [3] The rapid development of nanotechnology and material sciences has led to a myriad of nanocarriers being explored for siRNA delivery, [4] and promoting the preclinical potential of siRNA in treating genetically based diseases. siRNA delivery carriers, such as cationic polymers, [5] are predominately amine-abundant and can compress siRNAs into nanoparticles via electrostatic interaction between positive-charged amine groups (NH 3 + ) of polymer and negative-charged phosphate group (PO 3 4− ) of siRNA. However, the abundant presence of charged biomacromolecules in blood, can interfere with the association between cationic polymers and siRNAs, [6] making siRNA nanomedicines that solely rely on electrostatic interaction for stabilization at risk of dissociation in vivo, thereby Small interfering RNA (siRNA) holds inherent advantages and great potential for treating refractory diseases. However, lack of suitable siRNA delivery systems that demonstrate excellent circulation stability and effective at-site delivery ability is currently impeding siRNA therapeutic performance. Here, a polymeric siRNA nanomedicine (3I-NM@siRNA) stabilized by triple interactions (electrostatic, hydrogen bond, and hydrophobic) is constructed. Incorporating extra hydrogen and hydrophobic interactions significantly improves the physiological stability compared to an siRNA nanomedicine analog that solely relies on the electrostatic interaction for stability. The developed 3I-NM@siRNA nanomedicine demonstrates effective at-site siRNA release resulting from tumoral reactive oxygen species (ROS)-triggered sequential destabilization. Furthermore, the utility of 3I-NM@siRNA for treating glioblastoma (GBM) by functionalizing 3I-NM@siRNA nanomedicine with angiopep-2 peptide is enhanced. The targeted Ang-3I-NM@siRNA exhibits superb blood-brain barrier penetration and potent tumor accumulation. Moreover, by cotargeting polo-like kinase 1 and vascular endothelial growth factor receptor-2, Ang-3I-NM@ siRNA shows effective suppression of tumor growth and significantly improved survival time of nude mice bearing orthotopic GBM brain tumors. New siRNA nanomedicines featuring triple-interaction stabilization together with inbuilt self-destruct delivery ability provide a robust and potent platform for targeted GBM siRNA therapy, which may have utility for RNA interference therapy of other tumors or brain diseases. siRNA DeliveryThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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confidence: 99%

ROS‐Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy

et al. 2019

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“…The co-localization ratio (%) is a commonly used index to measure DNA release [42,43], which was carried out by the following formula:…”

Section: Dissociation Kinetics Of Liposome and Dnamentioning

confidence: 99%

Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

Zhao

et al. 2020

Preprint

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Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the“proton sponge effect”of the lipid. Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

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“…Biodegradable block copolymer is a promising drug-carrier material, with physical and chemical properties that can be regulated by adjusting the block composition ratio or adding a new block that meets the requirements [11,18,19]. Degradable materials (polycaprolactone (PCL), polyglycolide (PGA), polylactide (PLA), poly(lactic-co-glycolic acid) (PLGA), etc.)…”

Section: Of 13mentioning

confidence: 99%

Biodegradable Redox-Sensitive Star Polymer Nanomicelles for Enhancing Doxorubicin Delivery

Guo

Wen

et al. 2019

Nanomaterials

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A typical amphiphilic star polymer adamantane-[poly(lactic-co-glycolic acid)-bis(2-carboxyethyl) sulfide-poly(ethylene glycol) monomethyl ether)]4 with a specific hydrophilic/redox-sensitive/hydrophobic structure was designed and synthesized through ring opening and esterification reactions. The self-assembled nanomicelles were used as doxorubicin (DOX) delivery vehicles with suitable critical micelle concentrations (5.0 mg/L). After the drug being loaded, drug-loaded micelles showed good drug-loading efficiency (10.39%), encapsulation efficiency (58.1%), and drug release (up to 60%) under simulated biological environment conditions. In addition, the backbone structure of the biodegradable polymer was easily hydrolyzed by the action of biological enzymes. As expected, cell-based studies showed that the designed polymer micelles possessed good biocompatibility (a survival rate of 85% for NH-3T3 cells). Moreover, the drug (DOX) still maintained good anti-cancer effects after being loaded, which caused 40% of MCF-7 cells to survive. These redox-sensitive micelles showed anti-tumor therapeutic potential.

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Effects of hydrophobic core components in amphiphilic PDMAEMA nanoparticles on siRNA delivery

Cited by 63 publications

References 51 publications

ROS‐Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy

ROS‐Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy

Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

Biodegradable Redox-Sensitive Star Polymer Nanomicelles for Enhancing Doxorubicin Delivery

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