Peptide-drug conjugate endocytosis intracellular traffic

Cancer is one of the leading causes of death, accounting for about half a million deaths every year. Despite the ability of chemotherapy to improve cancer-related mortality, a significant proportion of cancer patients suffer from acquired drug resistance or relapse after long-term chemotherapy treatment. In contrast to chemotherapy, targeted therapy is considered a more efficacious and safer form of cancer treatment and has gained increasing interest in recent years

To achieve targeted therapy, drugs can be specifically delivered to a target tumor cell by coupling them to a peptide selected for its ability to bind to and enter the target cell. Such “Peptide-Drug-Conjugate” (PDC) complexes can enter mammalian cells through one of the several endocytic pathways. Our laboratory has already developed PDCs for several types of cancers. However, information is lacking as to how these complexes actually enter their target cells and their intracellular trafficking pathways and fate. The aim of this research is to provide this information and then to examine if there are common characteristics in uptake and intracellular trafficking between different PDCs.

We select an experimental system and study the endocytic pathways. Endocytic pathways include those that are dependent on the clathrin coat (CDE) or independent of clathrin (CIE). Most of the current information on cellular uptake of delivery vehicles is based on data following the use of chemical inhibitors of endocytic pathways and use siRNA to inhibit some of protein that dependent of different endocytic pathways .We chose to work with a five peptides that uptake of Human prostate cancer cell PC3. The results show that the most of PDCs uptake across CIE.

Finally, we finish research the endocytic pathways of PDCs, we begin to study the intracellular trafficking of our PDCs.