Title
New physical and chemical approaches for the cytosolic delivery of bio- therapeutics and nanoparticles into cells
Conference Dates
June 5-9, 2018
Abstract
Delivery of bio-therapeutics and nanomaterials into living cells is an important step not only for cell studies but also for therapy and bio-imaging. Clear examples are the intracellular delivery of various classes of nucleic acids (siRNA, µRNA, mRNA, pDNA), peptides and proteins for therapy purposes. As another example, all types of (inorganic/organic) nanoparticles are under investigation as intracellular labels for imaging purposes. Meanwhile it generally accepted that after uptake by cells, nanomaterials typically end up in endo-lysosomal vesicles in which they remain entrapped while they should escape from such compartments and arrive in the cytosolic fluids of the cells. In recent years our team undertook major efforts to understand the biophysics which play a role in (a lack of) escape of nanomaterials from endo-lysosomal vesicles. Vere recently we also discovered new chemical strategies (so named ‘escape adjuvants’) (1) which seems promising to ‘liberate’ nucleic acids (like siRNA) from endo-lysosomal vesicles into the cytosol. Furthermore we explored physical methods (either light (2,3) or ultrasound (4) driven) which directly deliver bio-therapeutics into the cytosol, thereby bypassing the endo-lysosomal routes. This lecture will explain our recent findings in this area, as reported in a serious of recently published papers (1-4). Both pharmaceutical, biological and engineering aspects of our work will be highlighted in the lecture.
References
1) Repurposing cationic amphiphilic drugs as adjuvants to induce lysosomal siRNA escape in nanogel transfected cells
F. Joris, L. De Backer, T. Van de Vyver, C. Bastiancich, S.C. De Smedt, K. Raemdonck
Journal of Controlled Release 2018, in Press
2) Comparison of gold nanoparticle mediated photoporation: vapour nanobubbles outperform direct heating for delivering macromolecules in live cells
R.H. Xiong, K. Raemdonck, K. Peynshaert, I. Lentacker, I. De Cock, J. Demeester, S.C. De Smedt, A.G. Skirtach, K. Braeckmans
ACS Nano 2014, 8(6): 6288-6296
3) Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inhentance and Enables Extended Quantitative in Vivo Cell Imaging
R.H. Xiong, F. Joris, S.Y. Liang, R. De Rycke, S. Lippens, J. Demeester, A. Skirtach, K. Raemdonck, U. Himmelreich, S.C. De Smedt, K. Braeckmans
Nano Letters 2016, 16(10): 5975-5986
4) Sonoprinting and the importance of microbubble loading for the ultrasound mediated cellular
delivery of nanoparticles
I. De Cock, G.P.R. Lajoinie, M. Versluis, S.C. De Smedt*, I. Lentacker
Biomaterials 2016, 83: 294-307
Recommended Citation
Stefaan De Smedt, K. Braeckmans, Koen Raemdonck, and Ine Lentacker, "New physical and chemical approaches for the cytosolic delivery of bio- therapeutics and nanoparticles into cells" in "Nanotechnology in Medicine II: Bridging Translational in vitro and in vivo Interfaces", Millicent Sullivan, PhD, University of Delaware, USA Josué Sznitman, Dr. Sc., Technion-Israel Institute of Technology, Israel Lola Eniola-Adefeso, PhD, University of Michigan, USA Srivatsan Kidambi, PhD, University of Nebraska - Lincoln, USA Eds, ECI Symposium Series, (2018). https://dc.engconfintl.org/nanotech_med_ii/41