| Multi-drug resistance (MDR) is one of the major problems of today's disease control and therapies, especially for the treatment of cancers. Lytic peptides, an abundant group of natural or artificial molecules killing cells through membrane disruption, can overcome MDR. But anti-cancer lytic peptides also have a fatal defect: deficiency of the selectivity between targets and normal tissues. My thesis focuses on constructing lytic peptides with tumor-selective killing ability.;Different strategies have been tried and applied. The first and the most effective approach, is to replace lysine or arginine residues by histidine ones. By this way, we have designed three series of lytic peptides based on three peptide templates. The second approach is to formulate ion-peptide complexes to control the activities of lytic peptides. The third approach is to produce pro-drug type of lytic peptides which can be activated by the specific enzymes over-expressed on surfaces of tumor cells. The fourth approach is to design lytic peptides with self-assembly feature. Positive and promising results have been obtained from both in vitro and in vivo studies. In addition, detailed acting mechanisms of the different lytic peptides have also been studied. |
