engleski

Specific targeted drugs delivery by TAT-technology

The importance of drug delivery is pivotal in the wide area of pharmacological research and it has not been solved yet. The main goal of every drug delivery system is the delivery of a precise amount of a drug to the desired location in order to achieve the necessary drug concentration in the targeted organ for effective treatment. Proteins and peptides are useful research and therapeutic tools, however their applications are limited because delivery to the desired location is not easily achievable. Process of protein transduction, using TAT-technology, allows the delivery of drugs and genetic materials inside the cells. This process occurred in a rapid, concentration-dependent fashion that appears to be independent of the receptors and transporters. It has broad implications in experimental systems for regulating intracellular processes and has the potential to be used in the development of new therapeutic strategies for cancer, infectious diseases, and development of vaccines. Cancer is the result of an imbalance among cell cycle progression and cell death, what is a reason that cancer research is increasingly focused on cell cycle and cell death regulatory mechanism. Apoptosis is genetically controlled form of cell death, with a distinctive role in both the development and prevention of cancer. It could be induced by a variety of anticancer drug. It is now well established that the reduced capacity of cancer cells of undergoing apoptosis is the main point in the pathogenesis and progression of large number of neoplasis as well as in therapeutic treatment failure. Drugs, with capability to target specific molecules are very attractive in treatment of cancer. Hyper proliferation of cancer cells is associated with deregulation of cell cycle progression, which is driven by the activities of CDKs. A key regulator of their activities is a p27 protein. It has significant role in cancer progression and antitumor drug response. To examine p27 as specific target molecule and its role in tumor cells apoptosis, protein transduction method is very suitable. This protein plays an important role in the arrest of the cell cycle and in communication between the extracellular signals and cell cycle controlling mechanism. To examine p27 as specific target molecule and its role in tumor cells apoptosis, transduction of TAT-p27, TAT-ptp27 and TAT-N'p27 was performed. It was shown that different forms of TAT-p27 protein can modulate the cell cycle of cultured cell lines and induced apoptosis, depending on the concentration and type of the cells. Also was shown that different signal transduction pathways were involved in induction of apoptosis. Thus, p27 could be used as a specific target for regulation of cell cycle and apoptosis in tumor cells. To introduce extraxellular p27 into the cells, protein transduction could be very useful. This method could give an opportunity for delivering of drugs into cells with emphasis on specific target molecules and result with major clinical improvement in curing cancer and similar diseases.

drug delivery; TAT-technology; p27; apoptosis

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