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首页> 外文期刊>Nanotechnology >Recruiting potent membrane penetrability in tumor cell-targeted protein-only nanoparticles
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Recruiting potent membrane penetrability in tumor cell-targeted protein-only nanoparticles

机译：在肿瘤细胞靶向蛋白纳米粒子中募集有效膜渗透性

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摘要

The membrane pore-forming activities of the antimicrobial peptide GWH1 have been evaluated in combination with the CXCR4-binding properties of the peptide T22, in self-assembling protein nanoparticles with high clinical potential. The resulting materials, of 25 nm in size and with regular morphologies, show a dramatically improved cell penetrability into CXCR4(+) cells (more than 10-fold) and enhanced endosomal escape (the lysosomal degradation dropping from 90% to 50%), when compared with equivalent protein nanoparticles lacking GWH1. These data reveal that GWH1 retains its potent membrane activity in form of nanostructured protein complexes. On the other hand, the specificity of T22 in the CXCR4 receptor binding is subsequently minimized but, unexpectedly, not abolished by the presence of the antimicrobial peptide. The functional combination T22-GWH1 results in 30% of the nanoparticles entering cells via CXCR4 while also exploiting pore-based uptake. Such functional materials are capable to selectively deliver highly potent cytotoxic drugs upon chemical conjugation, promoting CXCR4-dependent cell death. These data support the further development of GWH1-empowered cell-targeted proteins as nanoscale drug carriers for precision medicines. This is a very promising approach to overcome lysosomal degradation of protein nanostructured materials with therapeutic value.
机译：在具有高临床电位的自组装蛋白纳米粒子中，已经与肽T22的CXCR4结合性组合评估了抗微生物肽GWH1的膜孔形成活性。所得物质为25nm的大小和常规形态，显示出直接改善的细胞渗透性进入CXCR4（+）细胞（超过10倍），增强的内体逸出（溶酶体降解从90％滴加至50％），与缺乏GWH1的等效蛋白纳米颗粒相比。这些数据显示，GWH1以纳米结构蛋白质复合物的形式保留其有效膜活性。另一方面，随后，CXCR4受体结合中T22的特异性最小化，但出乎意料地，不通过抗微生物肽的存在消除。功能组合T22-GWH1导致30％的纳米颗粒通过CXCR4进入细胞，同时也利用基于孔的摄取。这种功能材料能够在化学缀合时选择性地提供高效的细胞毒性药物，促进CXCR4依赖性细胞死亡。这些数据支持GWH1动力的细胞靶向蛋白的进一步发展，作为纳米级药物载体，用于精密药物。这是一种非常有希望的方法来克服具有治疗价值的蛋白质纳米结构材料的溶酶体降解。

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