scholarly journals Shielding of Lipid Nanoparticles for siRNA Delivery: Impact on Physicochemical Properties, Cytokine Induction, and Efficacy

2014 ◽  
Vol 3 ◽  
pp. e210 ◽  
Author(s):  
Varun Kumar ◽  
June Qin ◽  
Yongfeng Jiang ◽  
Richard G Duncan ◽  
Benjamin Brigham ◽  
...  
2016 ◽  
Vol 24 (4) ◽  
pp. 788-795 ◽  
Author(s):  
Yusuke Sato ◽  
Hiroto Hatakeyama ◽  
Mamoru Hyodo ◽  
Hideyoshi Harashima

2016 ◽  
Vol 229 ◽  
pp. 48-57 ◽  
Author(s):  
Yusuke Sato ◽  
Yusuke Note ◽  
Masatoshi Maeki ◽  
Noritada Kaji ◽  
Yoshinobu Baba ◽  
...  

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Thai Thanh Hoang Thi ◽  
Estelle J. A. Suys ◽  
Jung Seok Lee ◽  
Dai Hai Nguyen ◽  
Ki Dong Park ◽  
...  

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1681
Author(s):  
Patrick Connerty ◽  
Ernest Moles ◽  
Charles E. de Bock ◽  
Nisitha Jayatilleke ◽  
Jenny L. Smith ◽  
...  

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.


Theranostics ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 192-203 ◽  
Author(s):  
Jinju Lee ◽  
Phei Er Saw ◽  
Vipul Gujrati ◽  
Yonghyun Lee ◽  
Hyungjun Kim ◽  
...  

Author(s):  
Andreia Jorge ◽  
Alberto Pais ◽  
Carla Vitorino

2017 ◽  
Vol 14 (10) ◽  
pp. 3290-3298 ◽  
Author(s):  
Yu Sakurai ◽  
Wataru Mizumura ◽  
Manami Murata ◽  
Tomoya Hada ◽  
Shoshiro Yamamoto ◽  
...  

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