Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China.
Biomater Sci. 2020 Mar 17;8(6):1759-1770. doi: 10.1039/c9bm01822k.
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.
目前，具有柔性蛋白壳和功能化修饰的生物工程化脱铁铁蛋白纳米笼已成为高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，在脱铁铁蛋白的 H 链亚基的 N 端修饰了不同数量的赖氨酸，得到了聚（L-赖氨酸）修饰的 H 链脱铁铁蛋白（nL-HFn）纳米笼，用于 siRNA 的递送和基因治疗。为了获得优异的细胞亲和力和摄取，纳米载体通过转铁蛋白受体介导的内吞作用被内化，然后从内涵体逃逸到细胞质中进行运输。与天然脱铁铁蛋白相比，赖氨酸修饰的负载 siRNA 的基因重组 NPs 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，赖氨酸修饰的生物工程化脱铁铁蛋白纳米笼可能是一种很有前途的核酸药物递送平台。
