Toxicity profiling of several common RNAi-based nanomedicines: a comparative study

Drug Delivery and Translational Research
Dalit Landesman-Milo, Dan Peer

Abstract

RNAi-based nanomedicine platforms (RNPs) have progressed from tools to study gene expression in vitro into clinical trials. Numerous RNPs strategies have been documented with an efficient ability to condense RNAi payloads and induce potent gene silencing. Moreover, some of these RNPs have been explored in various animal models, and some have even made it to the clinic. Still, there is lack of a clinically approved RNAi-based delivery strategy most probably due to unpredicted clinical toxicity. In this study, we prepared common RNPs such as cationic liposomes, polyamines, and hyaluronan-coated lipid-based nanoparticles and tested these strategies for global toxicity parameters such as changes in bodyweight, liver enzyme release, and hematological profiling. We found that polyamines such as polyethyleneimine and Poly-L-lysine released high levels of liver enzymes into the serum and reduced C57BL/6 mice bodyweight upon three intravenous injections. In addition, these polyamines dramatically reduced the total number of leukocytes, suggesting an immune suppression mechanism, while cationic liposomes, which also increased liver enzymes levels in the serum, elevated the total number of leukocytes probably by activation of Toll-like re...Continue Reading

References

May 6, 2003·Biochimica Et Biophysica Acta·Dan PeerRimona Margalit
Dec 4, 2003·Biochemical and Biophysical Research Communications·Mouldy Sioud, Dag R Sørensen
Dec 30, 2003·International Journal of Cancer. Journal International Du Cancer·Dan Peer, Rimona Margalit
Jul 17, 2004·Neoplasia : an International Journal for Oncology Research·Dan Peer, Rimona Margalit
Apr 6, 2005·Biochemical and Biophysical Research Communications·Zheng MaSong Li
Apr 14, 2005·Blood·Carol A Sledz, Bryan R G Williams
Jul 26, 2005·Nature Biotechnology·David V MorrisseyBarry Polisky
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Dan PeerMotomu Shimaoka
Jun 2, 2007·Nature Reviews. Drug Discovery·Antonin de FougerollesJudy Lieberman
Apr 29, 2008·Nature Biotechnology·Akin AkincDaniel G Anderson
Aug 5, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sumio ChonoLeaf Huang
Apr 30, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Shan GaoJørgen Kjems
Jul 22, 2009·The Journal of Clinical Investigation·Juan R Cubillos-RuizJose R Conejo-Garcia
Dec 10, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sang-Soo KimPremlata Shankar
Jan 12, 2010·Journal of Internal Medicine·B OzpolatG Lopez-Berestein
Jul 8, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yunching ChenLeaf Huang
Sep 14, 2010·Trends in Biotechnology·Monica R LaresDominique L Ouellet
Oct 16, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sabrina HöbelAchim Aigner
Apr 15, 2011·Gene Therapy·D Peer, J Lieberman
Jul 13, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shoshy MizrahyDan Peer
Sep 13, 2011·Methods in Molecular Biology·Noa Ben-ArieDan Peer
Oct 11, 2011·Nature Biotechnology·Florian LeuschnerMatthias Nahrendorf
Nov 30, 2011·Nanomedicine·Meir GoldsmithDan Peer
Dec 22, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jianfeng GuoCaitriona O'Driscoll
Jan 11, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dalit Landesman-Milo, Dan Peer
Sep 1, 2012·Cancer Letters·Dalit Landesman-MiloDan Peer
Sep 15, 2012·Advanced Drug Delivery Reviews·Ala Daka, Dan Peer
Feb 21, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yang LiuEn-Hua Wang

❮ Previous
Next ❯

Citations

Jan 17, 2016·Current Opinion in Biotechnology·Manu Smriti Singh, Dan Peer
Jan 7, 2016·Bioconjugate Chemistry·Dalit Landesman-Milo, Dan Peer
Dec 1, 2015·Small·Daniel F MoyanoVincent M Rotello
Oct 6, 2015·ACS Central Science·Hanxiang ZengZhibin Guan
Nov 17, 2015·Nature Reviews. Drug Discovery·Jonathan E Zuckerman, Mark E Davis
Aug 19, 2015·Nature Reviews. Genetics·Anders Wittrup, Judy Lieberman
May 8, 2015·Cancer Metastasis Reviews·Dalit Landesman-MiloDan Peer
Apr 1, 2016·Journal of Drug Targeting·Srinivas RamishettiDan Peer
Jul 21, 2017·ACS Nano·Stephanie Rietwyk, Dan Peer
Apr 18, 2018·Tissue Engineering. Part a·Siddharth PatelLuiz E Bertassoni
Feb 6, 2020·Pharmaceutics·Abishek WadhwaAneesh Thakur
Mar 4, 2020·Nanoscale·Pingsai LungQuan Li
Aug 15, 2020·Expert Opinion on Drug Delivery·L Gallego, V Ceña
Jan 27, 2021·Vaccines·Larisa I KarpenkoAlexander A Ilyichev
Feb 14, 2021·Biomaterials·Fangmin ChenHaijun Yu
Sep 22, 2020·Advanced Drug Delivery Reviews·Christian G Figueroa-EspadaRachel S Riley
Jun 20, 2021·Small·Xin FuXiaoli Zhu
Aug 4, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Javier T Granados-Riveron, Guillermo Aquino-Jarquin
Jan 4, 2017·Bioconjugate Chemistry·Mikhail V ZyuzinWolfgang J Parak
Aug 18, 2021·Advanced Drug Delivery Reviews·Maria L IbbaPaloma H Giangrande
May 8, 2019·Molecular Pharmaceutics·Keith Henry MossMaria Taskova
Aug 21, 2021·International Journal of Pharmaceutics·Qi ShuaiYunfeng Yan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Journal of Controlled Release : Official Journal of the Controlled Release Society
Ram DvashDan Peer
Journal of Controlled Release : Official Journal of the Controlled Release Society
Dalit Landesman-Milo, Dan Peer
© 2021 Meta ULC. All rights reserved