Eriksson Mathilda, Hassan Saadia, Larsson Rolf, Linder Stig, Ramqvist Torbjörn, Lövborg Henrik, Vikinge Trine, Figgemeier Egbert, Müller Jürgen, Stetefeld Jörg, Dalianis Tina, Ozbek Suat
Karolinska Institutet, Department of Oncology-Pathology, Cancer Center Karolinska R8:01, Karolinska University Hospital, 171 76 Stockholm.
Anticancer Res. 2009 Jan;29(1):11-8.
The nano-sized right-handed coiled-coil (RHCC) protein, originating from the archaebacterium Staphylothermus marinus, is stable at high salt concentrations, high temperatures, high pressures and extremes of pH. Its crystal structure reveals four hydrophobic cavities which can incorporate heavy metals. Nano-sized compounds have been used to carry cytotoxic drugs to tumours, avoiding delivery to healthy tissue, in part due to enhanced permeability in tumour blood vessels (enhanced permeability and retention effect).
The ability of RHCC to carry the platinum-containing chemotherapeutic drug cisplatin to cells, while retaining the cytotoxic potential was tested both in vitro and in vivo.
RHCC was able to bind and enter cells in vitro and was not severely toxic or immunogenic in mice. Moreover, RHCC incorporated cisplatin, without inhibiting the cytotoxic potential of the drug against tumour cell lines in vitro or in vivo.
RHCC can be used as a carrier of cisplatin without abrogating the effect of the drug.
源自嗜热栖热放线菌的纳米级右手卷曲螺旋(RHCC)蛋白在高盐浓度、高温、高压和极端pH值条件下均保持稳定。其晶体结构显示有四个可容纳重金属的疏水腔。纳米级化合物已被用于将细胞毒性药物输送至肿瘤,避免输送至健康组织,部分原因是肿瘤血管的通透性增强(增强渗透和滞留效应)。
测试了RHCC携带含铂化疗药物顺铂至细胞的能力,同时在体外和体内保留细胞毒性潜力。
RHCC在体外能够结合并进入细胞,且对小鼠无严重毒性或免疫原性。此外,RHCC掺入顺铂后,在体外或体内均未抑制该药物对肿瘤细胞系的细胞毒性潜力。
RHCC可作为顺铂的载体,而不会消除药物的作用。