TransPeptid – A research project within the program Pro FIT of the IBB
Transport systems for intracellular acting peptide therapeutics for the diagnosis and treatment of leukemic and solid tumors
Despite advances in the elucidation of the causes of tumor diseases, the benefits of new, drug-based treatment approaches are often inadequate and accompanied by many side effects. One important reason for the lack of efficacy of new drugs is that these drugs have so far not influenced key growth mechanisms because they only work outside the cell. The tumor cell membrane is often a barrier that is difficult to overcome for peptide- or protein-based drugs. When they can cross the tumor cell membrane, they are usually endosomally resorbed and degraded into lysosomes.
Therefore, the subject of the project is the establishment and validation of the technology for intracellular transport of molecules, which specifically interfere with the cell metabolism of tumor cells, the conjugation of these molecules with MacroDel™ substances and proof-of-principle investigations in in vitro and in vivo tumor models.
MacroDel™ molecules include polysulfated dendrimers with different branch structures. The special structure and charge of these molecules make it possible to transport conjugated drugs via specific mechanisms through the cell membrane into the cytosol of the target cells. This is intended to achieve accumulation and efficiency of conjugated effectors, such as peptides, proteins, cytostatics or fluorescent dyes, in tumor cells and tissues. The conjugates are transported directly to the cytoplasm via cell- and tissue-specific drug transporters. This transport route ensures that the therapeutic molecules reach the site of action directly and become active immediately.
Since these drug transporter proteins are expressed specifically in tumor tissue, it has been deliberated that the mechanism performs specific effects in therapy of cancer. The development of a novel target-specific class of substances can serve as a platform technology for scientific research and drug discovery.