Abstract
The group II chaperonin thermosome (THS) is a hollow protein nanoparticle that can encapsulate macromolecular guests. Two large pores grant access to the interior of the protein cage. Poly(amidoamine) (PAMAM) is conjugated into THS to act as an anchor for small interfering RNA (siRNA), allowing to load the THS with therapeutic payload. THS–PAMAM protects siRNA from degradation by RNase A and traffics KIF11 and GAPDH siRNA into U87 cancer cells. By modification of the protein cage with the cell-penetrating peptide TAT, RNA interference is also induced in PC-3 cells. THS–PAMAM protein–polymer conjugates are therefore promising siRNA transfection reagents and greatly expand the scope of protein cages in drug delivery applications.
| Original language | English |
|---|---|
| Article number | 1600046 |
| Number of pages | 10 |
| Journal | Advanced Science |
| Volume | 3 |
| Issue number | 10 |
| Early online date | 27 May 2016 |
| DOIs | |
| Publication status | Published - 1 Oct 2016 |
Funding
The authors thank Janine Zankel (Biozentrum, University of Basel) for help with FACS, Alessandro Potenza for help in the lab, Vesna Oliveri (ZMB, University of Basel) for TEM expertise, Thomas Mindt (University Hospital Basel) for inspiring discussions, Henning Stahlberg (C-CINA, Biozentrum, University of Basel) and Wolfgang Meier (Department of Chemistry, University of Basel) for their support. The authors thank the Marie-Curie Actions of the European Commission, the Holcim Stiftung Wissen, the Swiss National Science Foundation, the Swiss Nanoscience Institute, and the University of Basel SystemsX.ch RTD CINA for generous financial support.
Keywords
- drug delivery nanosystems
- nucleotide delivery vehicle
- protein cages
- protein–polymer conjugates
- RNA interference
- small interfering RNA