新型纳米颗粒精确靶向CXCR4阳性结直肠癌细胞
创作:Sophia 审核:Lexi 2019年10月14日
  • 将靶向CXCR4的T22肽、绿色荧光蛋白(GFP)、纳米颗粒组装成分H6构建成靶向CXCR4阳性细胞的纳米颗粒;
  • 通过CXCR4阳性HeLa细胞荷瘤小鼠实验验证,在该纳米颗粒的基础上增加内体逃逸肽HA2能增强纳米颗粒的靶向效果;
  • 在不同位置插入HA2内体逃逸肽会影响该多肽的活性;
  • 使用CXCR4拮抗剂能阻断纳米颗粒在肿瘤区域的积累,证实T22靶向肽的靶点是CXCR4;
  • 该蛋白纳米载体特异性靶向CXCR4阳性癌细胞,有望成为高效抗癌治疗新策略。
主编推荐语
Lexi
最新发表于Acta Biomaterialia的研究,通过适当选择功能肽和合适的调节位点,研究出一款多功能蛋白纳米颗粒,可精确靶向CXCR4阳性细胞,具有相关核内体逃逸能力。相关荷瘤小鼠体内实验证明该纳米颗粒对结直肠癌治疗的有效性。该研究也证明了增强蛋白质材料的非特异性膜活性不一定妥协于选择性细胞靶向,但可通过附带的功能模块改善选择性细胞靶向。
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Acta Biomaterialia [IF:7.242]

Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer

协同膜活性与受体依赖性肿瘤细胞靶向帮助纳米颗粒精确靶向CXCR4阳性结直肠癌

10.1016/j.actbio.2019.09.002

2019-09-05, Article

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By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4+ cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4+ colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4+ tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module.

First Authors:
Rita Sala,Laura Sánchez-García

Correspondence Authors:
Ramón Mangues,Antonio Villaverde

All Authors:
Rita Sala,Laura Sánchez-García,Naroa Serna,María Virtudes Céspedes,Isolda Casanova,Mònica Roldán,Alejandro Sánchez-Chardi,Ugutz Unzueta,Esther Vázquez,Ramón Mangues,Antonio Villaverde

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