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Therapeutic artificial organelles

Prerequisites for the research topics

We are experts in the determination of protein/enzyme locations and membrane permeability for polymeric vesicles by various analytical methods. Thus, the preferred location of biomacromolecules determined orchestrates the potential application of polymeric vesicles (Figure 1). Beside this, the pH-responsiveness of polymeric vesicles membrane plays an important role to use enzymatic nanoreactors for switch on and off enzymatic reactions.

Figure 1. Different protein and enzyme locations 1-4 in polymeric vesicles can be realized by the use of in-situ and post loading processes.
Figure 2. Biological action of MMPsomes for recovering fibrotic liver.

Enzyme-loaded polymeric vesicles as protein therapeutics

The unification of both key characteristics, e.g. enzyme location at polymeric vesicles and pH-responsiveness of polymeric vesicles, is required to establish protein therapeutics within and outside of cells and therapeutics with targeting properties. For extracellular matrix therapeutics preferred location of enzymes can be 4 and 3 (Figure 1). For example, Liver fibrosis affects millions of people. Excessive accumulation of aberrant extracellular matrix (ECM) proteins, mostly collagens, produced by activated hepatic stellate cells (HSCs), is a hallmark of liver fibrosis. We hypothesized that delivery of matrix metalloproteinase-1 (MMP-1) might potentiate collagen degradation and attenuate fibrosis development. Thus, MMP-1 loaded polymersomes (MMPsomes) were fabricated to validate our working hypothesis. In conclusion, our results demonstrate an innovative approach of MMP-1 delivery, using surface-decorated MMPsomes by Post Loading, for alleviating liver fibrosis (Figure 2).

Further investigations are in progress:

  • Lysosome-like organelles or for degradation of peptides.
  • Study of enzyme-loaded polymersomes in different body-like fluids and in presence of peptidases.
  • (Surface-)Functionalisation of enzyme-loaded polymersomes.

Further investigations are in progress:

  • Lysosome-like organelles or for degradation of peptides.
  • Study of enzyme-loaded polymersomes in different body-like fluids and in presence of peptidases.
  • (Surface-)Functionalisation of enzyme-loaded polymersomes.

Responsible Scientists at RP

Project Co-Leader

Dr. Dietmar Appelhans
+49-351-4658-353 +49-351-4658-565

Project Co-Leader

Dr. Silvia Moreno
+49-351-4658-494 +49-351-4658-565

Selected Publications

1) Journal Controlled Release 332 (2021) 594-607. DOI: 10.1016/j.jconrel.2021.03.016

2) Macromolecular Bioscience (2021) 2100102, DOI: 10.1002/mabi.202100102