Development mitochondrial destabilizing polypeptide inducing immunogenic cell death for enhanced caner immunotherapy
발표자
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초록
내용
Therapeutic drugs for cancer therapies have critical drawbacks, poor water soluble and obstacles about delivery to cytosol. Mitochondrial destabilizing polypeptides (MDPs) can disrupt mitochondrial membrane due to targeting motif. They can induce mitochondrial reactive oxygen species for immunogenic cell death (ICD). Synthesizing MDPs, elongated lysine and modified with trimethylamine (TMA) and triethylamine (TEA), mitochondrial targeting motives. Despite the low toxicity of TEA polypeptide, its efficacy showed potential as an ICD inducer comparable or superior to that of TMA polypeptide. The MDPs were treated on CT26 and demonstrate markers for mitochondrial stress, ROS and ICD. However, the performance for ICD of TEA modified MDP was remarkable comparing with TMA group, such as, CRT exposure, and HMGB1 and ATP release. Both of MDPs are outstanding self-delivery ICD inducing drug. It can also be utilized with various negative charged anticancer drugs by conforming polyplex with MDPs.