Unravelling biological barriers to nanomedicines

In drug delivery, intensive research is being carried out to develop ‘intelligent’     nanocarriers that are capable of efficiently delivering biopharmaceuticals to target cells. Obtaining a better insight in the ability of nanomedicines in crossing biological barriers that are of relevance to the delivery process is required to achieve efficient optimization of their structure and composition. Since about 10 years we are investigating the dynamic interaction of nanomedicines with various biological tissues. Special attention has gone to determining the colloidal stability of nanomedicine formulations in undiluted biological fluids, such as blood. Other studies have focused on characterizing nanomedicine mobility in extracellular tissues like cystic fibrosis mucus or vitreous humour. Also cellular uptake and intracellular processing of nanomedicines has been investigated in great detail. By providing a better insight into the stability and transport of nanoparticles during the various phases of the delivery process through the use of advanced microscopy techniques, it is our aim to enable a more efficient and rational development of improved carrier materials for the delivery of nucleic acids.

Selected key publications:

  • Lotte M.P. Vermeulen, Toon Brans, Stefaan C. De Smedt, Katrien Remaut, Kevin Braeckmans. Methodologies to Investigate Intracellular Barriers for Nucleic Acid Delivery in Non-viral Gene Therapy. Nano Today 21, 74-90 (2018).
  • Vermeulen L., Brans T., Samal S., Dubruel P., Demeester Jo., De Smedt S., Remaut K., Braeckmans K. Endosomal Size and Membrane Leakiness Influence Proton Sponge-Based Rupture of Endosomal Vesicles. ACS Nano 12, 2332-2345 (2018).
  • Martens T.F., Remaut K., Deschout H., Engbersen J.F.J., Hennink W.E., van Steenbergen M.J., Demeester J., De Smedt S.C., Braeckmans K. Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy. J. Control. Release 202, 83-92 (2015).
  • Forier K., Messiaen A.S., Raemdonck K., Nelis H., De Smedt S.C., Demeester J., Coenye T., Braeckmans K. Probing the size limit for nanomedicine penetration into Burkholderia multivorans and Pseudomonas aeruginosa biofilms. J. Control. Release 195, 21-28 (2014).
  • Vercauteren  D., Piest M., van der Aa L.J., Al Soraj M., Jones A.T., Engbersen J.F.J., De Smedt S.C., Braeckmans K. Flotillin-dependent endocytosis and a phagocytosis-like mechanism for cellular internalization of disulfide-based poly(amido amine)/DNA polyplexes. Biomaterials 32, 3072-3084 (2011).
  • Vercauteren D., Deschout H., Remaut K., Engbersen J.F.J., Jones A.T., Demeester J., De Smedt S.C., Braeckmans K. Dynamic Colocalization Microscopy to Characterize Intracellular Trafficking of Nanomedicines. ACS Nano 5, 7874-7884 (2011).

For more information on ongoing projects, please contact: