Successful and effective cellular delivery remains a main obstacles in the medical field. The use of
cell-penetrating peptides (CPPs) has become one of the most important tools for the internalisation of a wide range of molecules including pharmaceuticals. It is still difficult to choose one
CPP for one biological application because there is no ubiquitous
CPP meeting the diverse requirements. In our case, we are looking for a suitable
CPP to deliver the pro-apoptotic
KLA peptide (KLAKLAKKLAKLAK) by a simple co-incubation strategy. For that reason, we selected three different cell lines (fibroblastic, cancerous and macrophagic cells) and studied the uptake and subcellular localisation of six different CPPs alone as well as mixed with the
KLA peptide. Furthermore, we used the CPPs with a carboxyamidated or a carboxylated C-terminus and analysed the impact of the C-termini on internalisation and cargo delivery. We could clearly showed that the cellular
CPP uptake is not only dependent on the used
CPP and cell line but also highly affected by its chemical nature of the C-terminus (uptake: carboxyamidated CPPs > carboxylated CPPs) and can influence its cellular localisation. We successfully delivered the
KLA peptide in the three cell lines and learned that here as well, the C-terminus is crucial for an effective
peptide delivery. Finally, we induced apoptosis in mouse leukaemic monocyte macrophage (RAW 264.7) and in human breast
adenocarcinoma (MCF-7) cells using the mixture of amidated MPG peptide : KLA and in african green monkey kidney fibroblast (Cos-7) cells using carboxylated
integrin peptide : KLA.