Surface Modification

Surface Modification

The modular LbL construction allows a surface functionalization of the carriers independent of their internal design. Such a modification can be used to facilitate specific or enhanced uptake but may also be applied to protect the inner structure from opsonization or early degradation during carrier transport.

Focus on:

  • Carrier shielding and protection

    • Lipid membrane
    • Integration of functional lipids
    • Combination of different surface functionalities

  • Enhanced uptake

    • Cell-penetrating peptides
    • Virus-like particles

  • Specific uptake

    • Antibodies

1. Shielding of the Microcarrier's Inner Structure and Functionalization towards Specific Uptake: Lipid Membrane and Antibodies

The targeted addressing of specific cells is another important issue in microcarrier functionalization in order to transport defined amounts of active agents as well as to avoid unintended side-effects in other cells within the tissue. The objectives here are focused on the specific uptake of LbL carriers by cells, with emphasis placed on an enhanced biocompatibility and minimization of non-specific interactions with biological systems. Biocompatibility and protective function can be obtained by a homogeneously and tightly assembled phospholipid membrane as a supported lipid layer on top of the underlying biopolymer multilayer(1). The integration of a functional lipid (e.g. phosphatidylethanolamine, PE) equipped with polyethylene glycol (PEG) enhances the shielding properties of the carrier. Biotinylated PEG can be used for the coupling of additional functional molecules via streptavidin/biotin binding(2). Thus, e.g. different antibodies can be assembled without disturbing the construction of the inner structure, since homogeneity and tightness of the lipid membrane depend strongly on the polymer material, lipid components, and assembly conditions(1).

2a. Fast Uptake of Microcarriers by Cells: Cell-Penetrating Peptides

Another aim is the enhancement of cellular uptake, for example by faster carrier incorporation by cells. A fast uptake is very important for drug delivery systems, since early and unintended carrer degradation in extracellular space may thus be reduced. Cell penetrating peptides, assembled as outermost layer, offer a good opportunity to enhance the uptake of carriers into cells(3).

2b. Enhanced Cell Entry of Microcarriers: Virus-like Particles

Enhanced uptake can also be initialized by virus-like particles assembled onto the LbL-carrier's surface. The fusion of enveloped virus-like particles with an underlying lipid membrane at low pH ensures embedding of the capsid and presentation of the fusion proteins on the overall surface(4,5). Although only shown with Rubella-like particles, the universal assembly technique allows the application of a wide variety of viral systems.

 

(4)  Fischlechner, M., Zschörnig, O., Hofmann, J., Donath, E. Engineering Virus Functionalities on Colloidal Polyelectrolyte Lipid Composites. Angew Chem Int Ed Engl. 44 (2005) 2892-2895. [DOI]

(5)   Fischlechner, M., Reibetanz, U., Zaulig, M., Enderlein, D., Romanova, J., Leporatti, S., Moya, S., Donath, E. Fusion of Enveloped Virus Nanoparticles with Polyelectrolyte-Supported Lipid Membranes for the Design of Bio/Nonbio Interfaces. Nano Lett. 7 (2007) 3540-3546. [DOI]

Funding

  • German Research Foundation (DFG, RE 2681/2-1)
  • PhD scholarship: ESF, European Union and the Free State of Saxony, supported by DFG graduate school 185 "Leipzig School of Natural Sciences Building with Molecules and Nono-objects" (BuildMoNa) (M. Göse)
  • Scholarship: Formel.1 program, Medical Faculty, Universität Leipzig

 

 

letzte Änderung: 08.06.2017