In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.
Drug resistance is an increasing problem in the treatment of vaginitis bacterial vaginosis and vulvovaginal candidiasis caused by biofilm-forming bacteria and fungi. In this study, the antimicrobial activities of the synergistic effects coordinated by antimicrobial peptides HPRP-A1, HPRP-A2, and chlorhexidine acetate (CHA), against biofilms caused by Gram-negative and Gram-positive bacteria, and one fungus Candida albicans , were investigated in vitro and in mouse and rat infection models. The minimal biofilm inhibitory concentration and the fractional biofilm inhibitory concentration of HPRP-A1, HPRP-A2 alone and in combination with CHA were determined by classical methods. The crystal violet staining assay was used to determine the biomass of agents on biofilms. The MTT assay was used to determine the metabolic activity of agents on biofilms. Different microscopy assays were used to observe the morphological characteristics of bacterial and fungal biofilms after drug treatments. The extracellular polysaccharide was detected by a phenol–sulfuric acid method. The combined uses of HPRP-A1, HPRP-A2 and CHA exerted strong synergistic effects to inhibit the formation of bacterial and fungal biofilms and disrupt the construction of biofilms in vitro and in vivo. In animal vaginitis models, the drug combination reduced 99.9% of the number of bacterial and fungal CFU, and showed significant therapeutic effects against biofilm vaginitis. The mechanism of membrane disruption coordinated by the combination of drugs depends not only on the inhibition of extracellular polysaccharides secreted by bacterial and fungal cells, but also on the ability of the peptides to penetrate the cell membrane.
危险品化学品经营许可证（带存储）