Mechanism of Macromolecular Structure Evolution in Self-Assembled Lipid Nanoparticles for siRNA Delivery

Langmuir ◽  
2014 ◽  
Vol 30 (16) ◽  
pp. 4613-4622 ◽  
Author(s):  
Marian E. Gindy ◽  
Katherine DiFelice ◽  
Varun Kumar ◽  
Robert K. Prud’homme ◽  
Robert Celano ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Lipid Nanoparticles ◽  
Structure Evolution ◽  
Macromolecular Structure ◽  
Self Assembled

scholarly journals Development of siRNA-Loaded Lipid Nanoparticles Targeting Long Non-Coding RNA LINC01257 as a Novel and Safe Therapeutic Approach for t(8;21) Pediatric Acute Myeloid Leukemia

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1681
Author(s):  
Patrick Connerty ◽  
Ernest Moles ◽  
Charles E. de Bock ◽  
Nisitha Jayatilleke ◽  
Jenny L. Smith ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Sirna Delivery ◽  
Standard Of Care ◽  
Lipid Nanoparticles ◽  
Protein Product ◽  
Peripheral Blood Mononuclear ◽  
Acute Myeloid

Standard of care therapies for children with acute myeloid leukemia (AML) cause potent off-target toxicity to healthy cells, highlighting the need to develop new therapeutic approaches that are safe and specific for leukemia cells. Long non-coding RNAs (lncRNAs) are an emerging and highly attractive therapeutic target in the treatment of cancer due to their oncogenic functions and selective expression in cancer cells. However, lncRNAs have historically been considered ‘undruggable’ targets because they do not encode for a protein product. Here, we describe the development of a new siRNA-loaded lipid nanoparticle for the therapeutic silencing of the novel oncogenic lncRNA LINC01257. Transcriptomic analysis of children with AML identified LINC01257 as specifically expressed in t(8;21) AML and absent in healthy patients. Using NxGen microfluidic technology, we efficiently and reproducibly packaged anti-LINC01257 siRNA (LNP-si-LINC01257) into lipid nanoparticles based on the FDA-approved Patisiran (Onpattro®) formulation. LNP-si-LINC01257 size and ζ-potential were determined by dynamic light scattering using a Malvern Zetasizer Ultra. LNP-si-LINC01257 internalization and siRNA delivery were verified by fluorescence microscopy and flow cytometry analysis. lncRNA knockdown was determined by RT-qPCR and cell viability was characterized by flow cytometry-based apoptosis assay. LNP-siRNA production yielded a mean LNP size of ~65 nm with PDI ≤0.22 along with a >85% siRNA encapsulation rate. LNP-siRNAs were efficiently taken up by Kasumi-1 cells (>95% of cells) and LNP-si-LINC01257 treatment was able to successfully ablate LINC01257 expression which was accompanied by a significant 55% reduction in total cell count following 48 h of treatment. In contrast, healthy peripheral blood mononuclear cells (PBMCs), which do not express LINC01257, were unaffected by LNP-si-LINC01257 treatment despite comparable levels of LNP-siRNA uptake. This is the first report demonstrating the use of LNP-assisted RNA interference modalities for the silencing of cancer-driving lncRNAs as a therapeutically viable and non-toxic approach in the management of AML.

scholarly journals Mono-arginine Cholesterol-based Small Lipid Nanoparticles as a Systemic siRNA Delivery Platform for Effective Cancer Therapy

Theranostics ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 192-203 ◽  
Author(s):  
Jinju Lee ◽  
Phei Er Saw ◽  
Vipul Gujrati ◽  
Yonghyun Lee ◽  
Hyungjun Kim ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Sirna Delivery ◽  
Lipid Nanoparticles ◽  
Delivery Platform ◽  
Effective Cancer Therapy

scholarly journals Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery

2012 ◽  
Vol 7 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Hyukjin Lee ◽  
Abigail K. R. Lytton-Jean ◽  
Yi Chen ◽  
Kevin T. Love ◽  
Angela I. Park ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Self Assembled

Observing Self-Assembled Lipid Nanoparticles Building Order and Complexity through Low-Energy Transformation Processes

ACS Nano ◽  
2009 ◽  
Vol 3 (9) ◽  
pp. 2789-2797 ◽  
Author(s):  
Xavier Mulet ◽  
Xiaojuan Gong ◽  
Lynne J. Waddington ◽  
Calum J. Drummond
Keyword(s):  
Lipid Nanoparticles ◽  
Low Energy ◽  
Energy Transformation ◽  
Self Assembled ◽  
Transformation Processes

scholarly journals Self-Assembled Cationic β-Cyclodextrin Nanostructures for siRNA Delivery

2019 ◽  
Vol 16 (3) ◽  
pp. 1358-1366 ◽  
Author(s):  
Raghvendra Pratap Singh ◽  
Tania Hidalgo ◽  
Pierre-Andre Cazade ◽  
Raphael Darcy ◽  
Michael F. Cronin ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Self Assembled

scholarly journals Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II) dipicolylamine)-Functionalized, Self-Assembled Nanoconjugate

2011 ◽  
Vol 51 (2) ◽  
pp. 445-449 ◽  
Author(s):  
Gang Liu ◽  
Ki Young Choi ◽  
Ashwinkumar Bhirde ◽  
Magdalena Swierczewska ◽  
Juan Yin ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Self Assembled

Targeted siRNA Delivery Using Lipid Nanoparticles

2019 ◽  
pp. 259-283
Author(s):  
Andreia Jorge ◽  
Alberto Pais ◽  
Carla Vitorino
Keyword(s):  
Sirna Delivery ◽  
Lipid Nanoparticles

scholarly journals Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells

2016 ◽  
Vol 24 (4) ◽  
pp. 788-795 ◽  
Author(s):  
Yusuke Sato ◽  
Hiroto Hatakeyama ◽  
Mamoru Hyodo ◽  
Hideyoshi Harashima
Keyword(s):  
Physicochemical Properties ◽  
Sirna Delivery ◽  
Lipid Nanoparticles ◽  
Liver Cells
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