Genetic recombination of poly(l-lysine) functionalized apoferritin nanocages that resemble viral capsid nanometer-sized platforms for gene therapy.,Biomaterials Science

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Genetic recombination of poly(l-lysine) functionalized apoferritin nanocages that resemble viral capsid nanometer-sized platforms for gene therapy.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-02-03 , DOI: 10.1039/c9bm01822k
Haiqin Huang ₁ , Shirui Yuan ₁ , Zhuo Ma ₁ , Peng Ji ₁ , Xiaonan Ma ₁ , Zhenghong Wu ₁ , Xiaole Qi ₁

Affiliation

Currently, bioengineered apoferritin nanocages with flexible protein shells and functionalized modifications have become an attractive approach for efficient anti-tumor therapy. Here, we modified the N-terminus of H-chain subunits in apoferritin with different amounts of lysine via genetic recombination to obtain a poly(l-lysine) modified H-chain apoferritin (nL-HFn) nanocage for siRNA delivery and gene therapy. To achieve excellent cellular affinity and uptake, the nanocarriers were internalized through transferrin receptor-mediated endocytosis, then escaped from the endosome for cytoplasmic transport. Compared with natural apoferritin, the siRNA-loaded genetic recombination NPs modified with lysine exhibit stronger RNA-interference and antitumor efficiency both in vitro and in 4T1 tumor model mice. Therefore, bioengineered apoferritin nanocages modified with lysine might be a promising platform for nucleic acid drug delivery.

中文翻译：

聚（l-赖氨酸）功能化的载铁蛋白纳米笼的基因重组，类似于病毒衣壳纳米大小的基因治疗平台。

当前，具有柔性蛋白壳和功能化修饰的生物工程脱铁铁蛋白纳米笼已成为有效抗肿瘤治疗的一种有吸引力的方法。在这里，我们通过基因重组用不同量的赖氨酸修饰了载铁蛋白中H链亚基的N末端，以获得用于siRNA递送和基因治疗的聚（L-赖氨酸）修饰的H链载铁蛋白（nL-HFn）纳米笼。为了获得优异的细胞亲和力和摄取，通过运铁蛋白受体介导的内吞作用将纳米载体内在化，然后从内体中逃逸出来进行细胞质转运。与天然载铁蛋白相比，用赖氨酸修饰的siRNA负载的基因重组NP在体外和4T1肿瘤模型小鼠中均表现出更强的RNA干扰和抗肿瘤效率。因此，

更新日期：2020-03-19

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