Nanomedicine Nanocarriers for gene and drug delivery
In the nanocarriers group, the aim is to (i) design, (ii) assemble, (iii) characterize, and (iv) evaluate the therapeutic potential, of soft self-assembled nanoparticles (i.e. nanocarriers) for gene and drug delivery. We use a wide array of techniques and bio-inspired ideas to assemble and characterize complex nanocarriers aimed to target specific/diseased cells/tissues, enter inside them, and deliver therapeutic nucleic acids or drugs at the desired location.
Particular emphasis is placed on the development of novel microfluidic-based methods to aid in the assembly process. These devices allow not only a versatile and automated way of producing nanocarrier particles of controlled size and distribution, but also to take advantage of the out-of-equilibrium nature of flow to further manipulate the materials and produce novel complex structures of therapeutic interest.
The typical work-flow in the laboratory consists in: (i) design and fabrication of microfluidic devices for nanocarrier assembly; (ii) formation of the nanocarrier systems under flow and formulation optimization; (iii) physicochemical and structural characterization of the produced nanocarriers with state-of-the-art tools (e.g. cryo-TEM and small-angle X-ray scattering - SAXS); and (iv) evaluation of the therapeutic potential of the resulting particles (i.e. measurements of transfection efficiency in different cell lines). Promising particles will also be tested in in-vivo systems at later stages.
Figure. Example of cationic liposome – DNA nanoparticle (CL-DNA NP) characterization. (a) Schematic of a CL-DNA NP functionalized with PEG (for enhanced blood circulation) and PEG-RGD ligands (for enhanced cellular uptake). In this example, the nanoparticles contain two lipid bilayers with DNA sandwiched between them. (b) Example of a dual-label fluorescence experiment. The co-localization of the two different dyes (one labeling DNA and the other the CL) confirms that CL and DNA have complexed and formed the new particles. (c) The structure of the particles can be assessed through SAXS. The number and position of Bragg peaks identifies the particle structure (in this case, layered) and the width of the peaks relates to the number of layers (in this case, two bilayers on average).
Group manager Bruno Silva