Single-Step Assembly of Cationic Lipid–Polymer Hybrid Nanoparticles for Systemic Delivery of siRNA

ACS Nano ◽  
2012 ◽  
Vol 6 (6) ◽  
pp. 4955-4965 ◽  
Author(s):  
Xian-Zhu Yang ◽  
Shuang Dou ◽  
Yu-Cai Wang ◽  
Hong-Yan Long ◽  
Meng-Hua Xiong ◽  
...  
Keyword(s):  
Cationic Lipid ◽  
Single Step ◽  
Hybrid Nanoparticles ◽  
Systemic Delivery ◽  
Polymer Hybrid

scholarly journals Nebulised lipid–polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells

2019 ◽  
Vol 5 (2) ◽  
pp. 00161-2018 ◽  
Author(s):  
Sebastian Vencken ◽  
Camilla Foged ◽  
Joanne M. Ramsey ◽  
Louise Sweeney ◽  
Sally-Ann Cryan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Double Emulsion ◽  
Cationic Lipid ◽  
Bronchial Epithelial Cells ◽  
Hybrid Nanoparticles ◽  
Bronchial Epithelial ◽  
Polymer Hybrid ◽  
Promising Strategy ◽  
Aerodynamic Properties ◽  
Endogenous Regulators

Modulation of microRNAs (miRNAs), endogenous regulators of gene expression, is a promising strategy for tackling inflammatory lung diseases. In this proof-of-concept study, we tested delivery of miR-17 to bronchial epithelial cells (BECs) using nebulised lipid–polymer hybrid nanoparticles (LPNs). The primary aim was to reduce the induced secretion of miR-17's target, i.e. the pro-inflammatory chemokine interleukin (IL)-8.Synthetic miR-17 mimics were loaded into LPNs composed of poly(dl-lactic-co-glycolic acid) (PLGA) and the cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP) using a double emulsion solvent evaporation method and nebulised using the Aerogen Solo nebuliser. The physicochemical, aerosol, inflammatory and cytotoxic properties of LPNs were characterised. The effect of LPNs on lipopolysaccharide (LPS)-induced IL-8 production from human NuLi-1 BECs was tested by ELISA.The z-average, polydispersity index and ζ-potential of the LPNs and the aerodynamic properties of nebulised suspensions were in a range optimal for deposition in the bronchi and bronchioles post-inhalation. Cytotoxic and pro-inflammatory effects were minimal for LPNs loaded with a model cargo. Nebulisation did not affect the physicochemical or functional properties of the LPNs. Nebulised miR-17-loaded LPNs downregulated LPS-induced IL-8 secretion by >40% in BECs.This study suggests that DOTAP-modified PLGA LPNs are efficient and well-tolerated carriers for delivery of miRNA mimics to BECs.

scholarly journals EPCT-25. SMO PROTEIN DEPLETION IN SHH MEDULLOBLASTOMAS USING MICROBUBBLE-ENHANCED ULTRASOUND AND SIRNA LOADED CATIONIC NANOPARTICLES

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i52-i52
Author(s):  
Yutong Guo ◽  
Hohyun Lee ◽  
Zhou Fang ◽  
Anastasia Velalopoulou ◽  
Jinhwan Kim ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Biological Fluids ◽  
Cationic Lipid ◽  
Physical Method ◽  
Cell Uptake ◽  
Hybrid Nanoparticles ◽  
Direct Result ◽  
Systemic Delivery ◽  
Protein Depletion

Abstract RNA-based therapies offer unique advantages for treating pediatric brain tumors. However, the systemic delivery remains a major problem due to degradation of unmodified RNA in biological fluids, poor brain accumulation, and poor cancer cell uptake or escape from the endosomal lipid bilayer barrier. While nanoparticle encapsulation can prolong circulation time and facilitate cellular uptake, their accumulation in brain tumor remains particularly poor due to their low permeability across the blood-brain barrier and limited intratumoral penetration. Focused ultrasound, when combined with circulating microbubbles (MB-FUS) provides a physical method to transiently modulate the brain tumor microenvironment (TME) and improve nanoparticle delivery. Here, we have examined the delivery of siRNA targeting the Smoothened (SMO) pathway, packaged in 50 nm cationic lipid-polymer hybrid nanoparticles (cLPH:siRNA-SMO), combined with MB-FUS in murine SmoA2 sonic hedgehog (SHH) medulloblastoma. At 30 hours after treatment, we observed the depletion of the SMO protein target, responsible for driving SHH medulloblastoma formation and growth, in mice that had received treatment with MB-FUS and cLPH:siRNA-SMO, but not with cLPH:siRNA-SMO alone. We also confirmed that SMO protein depletion was spatially achieved in the tumor regions with detected cLPH:siRNA-SMO using FISH assay, and that there was 15 fold induction of tumor cell apoptosis compared to tumors in mice that had received cLPH:siRNA-SMO alone. The limited induction of apoptosis was observed with either cLPH:siRNA (non-targeting) or MB-FUS and cLPH:siRNA (non-targeting), suggest that the observed apoptosis induction in the SmoA2 model was the direct result of SMO depletion rather than nonspecific effects of MB-FUS or cLPH:siRNA. Our findings provide a paradigm shift in drug delivery in brain tumors, where physical methods and nanotechnology are tuned together to develop rational strategies for the effective delivery of nucleic acids in brain tumors.

Development and characterization of single step self-assembled lipid polymer hybrid nanoparticles for effective delivery of methotrexate

RSC Advances ◽  
2015 ◽  
Vol 5 (77) ◽  
pp. 62989-62999 ◽  
Author(s):  
Neeraj K. Garg ◽  
Bhupinder Singh ◽  
Gajanand Sharma ◽  
Varun Kushwah ◽  
Rajeev K. Tyagi ◽  
...  
Keyword(s):  
Single Step ◽  
Controlled Delivery ◽  
Hybrid Nanoparticles ◽  
Polymer Hybrid ◽  
Effective Delivery ◽  
Self Assembled

The present study was designed to develop methotrexate (MTX) loaded lipid polymer hybrid nanoparticles (LPHNPs) for spatial and controlled delivery of this drug.

Quick Synthesis of Lipid−Polymer Hybrid Nanoparticles with Low Polydispersity Using a Single-Step Sonication Method

Langmuir ◽  
2010 ◽  
Vol 26 (22) ◽  
pp. 16958-16962 ◽  
Author(s):  
Ronnie H. Fang ◽  
Santosh Aryal ◽  
Che-Ming Jack Hu ◽  
Liangfang Zhang
Keyword(s):  
Single Step ◽  
Hybrid Nanoparticles ◽  
Polymer Hybrid

Lipid-polymer hybrid nanoparticles: Synthesis strategies and biomedical applications

2019 ◽  
Vol 160 ◽  
pp. 130-142 ◽  
Author(s):  
Vivek Dave ◽  
Kajal Tak ◽  
Amit Sohgaura ◽  
Ashish Gupta ◽  
Veera Sadhu ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Hybrid Nanoparticles ◽  
Polymer Hybrid ◽  
Nanoparticles Synthesis

scholarly journals Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2034 ◽  
Author(s):  
Christian D. Siewert ◽  
Heinrich Haas ◽  
Vera Cornet ◽  
Sara S. Nogueira ◽  
Thomas Nawroth ◽  
...  
Keyword(s):  
Small Angle ◽  
Messenger Rna ◽  
Physicochemical Characterization ◽  
Single Step ◽  
Model Systems ◽  
Molecular Organization ◽  
Hybrid Nanoparticles ◽  
Polymer Mixture ◽  
Internal Organization ◽  
Transfection Efficacy

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

2017 ◽  
Vol 28 (25) ◽  
pp. 255101 ◽  
Author(s):  
Cuiping Yao ◽  
Ming Wu ◽  
Cecheng Zhang ◽  
Xinyi Lin ◽  
Zuwu Wei ◽  
...  
Keyword(s):  
Hybrid Nanoparticles ◽  
Polymer Hybrid ◽  
Doxorubicin Release

A scalable and robust cationic lipid/polymer hybrid nanoparticle platform for mRNA delivery

2021 ◽  
pp. 121314
Author(s):  
Randall A. Meyer ◽  
G. Patrick Hussmann ◽  
Norman C. Peterson ◽  
Jose Luis Santos ◽  
Anthony D. Tuesca
Keyword(s):  
Cationic Lipid ◽  
Polymer Hybrid ◽  
Hybrid Nanoparticle
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