PDF(Pubmed)
Abstract：
CXCR4 is a cytokine receptor used by HIV during cell attachment and infection. Overexpressed in the cancer stem cells of more than 20 human neoplasias, CXCR4 is a convenient antitumoral drug target. T22 is a polyphemusin-derived peptide and an effective CXCR4 ligand. Its highly selective CXCR4 binding can be exploited as an agent for the cell-targeted delivery and internalization of associated antitumor drugs. Sharing chemical and structural traits with antimicrobial peptides (AMPs), the capability of T22 as an antibacterial agent remains unexplored. Here, we have detected T22-associated antimicrobial activity and biofilm formation inhibition over Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, in a spectrum broader than the reference AMP GWH1. In contrast to GWH1, T22 shows neither cytotoxicity over mammalian cells nor hemolytic activity and is active when displayed on protein-only nanoparticles through genetic fusion. Under the pushing need for novel antimicrobial agents, the discovery of T22 as an AMP is particularly appealing, not only as its mere addition to the expanding catalogue of antibacterial drugs. The recognized clinical uses of T22 might allow its combined and multivalent application in complex clinical conditions, such as colorectal cancer, that might benefit from the synchronous destruction of cancer stem cells and local bacterial biofilms.
摘要：
CXCR4是HIV在细胞附着和感染期间使用的细胞因子受体。在20多个人类肿瘤的肿瘤干细胞中过度表达，CXCR4是一种方便的抗肿瘤药物靶标。T22是多血丝素衍生的肽和有效的CXCR4配体。其高度选择性的CXCR4结合可用作相关抗肿瘤药物的细胞靶向递送和内化的试剂。与抗菌肽（AMP）共享化学和结构特征，T22作为抗菌剂的能力仍未被探索。这里,我们已经检测到T22相关的抗菌活性和生物膜形成抑制大肠杆菌，金黄色葡萄球菌和铜绿假单胞菌,在比参考AMPGWH1更宽的光谱中。与GWH1相反,T22既不显示对哺乳动物细胞的细胞毒性也不显示溶血活性,并且当通过遗传融合在仅蛋白质的纳米颗粒上显示时具有活性。在对新型抗菌剂的推动需求下，T22作为AMP的发现特别有吸引力，不仅仅是作为扩大的抗菌药物目录的补充。T22的公认临床用途可能允许其在复杂临床条件下的联合和多价应用。比如结肠直肠癌，这可能受益于癌症干细胞和局部细菌生物膜的同步破坏。
