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

Dalit Landesman-Milo, Dan Peer

Research output: Contribution to journalArticle

29 Scopus citations

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 receptors 2 and 4. Coating the liposomes with hyaluronan, a hydrophilic glycosaminoglycan, provided a protective layer and did not induce adverse effects upon multiple intravenous injections. These findings suggest that there is an urgent need to develop gold standards for nanotoxicity in the field of RNAi that will be embraced by the RNAi community.

Original languageEnglish (US)
Pages (from-to)96-103
Number of pages8
JournalDrug Delivery and Translational Research
Volume4
Issue number1
DOIs
StatePublished - Feb 1 2014

Keywords

  • Cationic liposomes
  • Nanomedicines
  • Nanotoxicity
  • Polyamines
  • RNAi

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Toxicity profiling of several common RNAi-based nanomedicines: A comparative study'. Together they form a unique fingerprint.

Cite this