Construction of DNA-displaying nanoparticles by enzymatic conjugation of DNA and elastin-like polypeptides using a replication initiation protein
Construction of DNA-displaying nanoparticles by enzymatic conjugation of DNA and elastin-like polypeptides using a replication initiation protein
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DOI：
10.1088/1361-6528/ab8042
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发表时间：
2020-04-03
期刊：
影响因子：
3.5
通讯作者：
Mie, Masayasu
中科院分区：
文献类型：
--
作者：
Guo, Wei;Mashimo, Yasumasa;Mie, Masayasu
开发了由单链DNA（ssDNA）和弹性蛋白样多肽（ELP）的缀合物组成的DNA展示纳米颗粒。ssDNA通过与ELP融合的猪圆环病毒2型复制起始蛋白（pRep）的催化结构域与ELP酶促缀合。由于ELP的疏水性和缀合的ssDNA的亲水性，在加热至高于相变温度的温度时形成纳米颗粒。我们通过将已知与粘蛋白1（MUC1）结合的DNA适体与ELP缀合，证明了所得纳米颗粒作为具有肿瘤靶向性质的药物载体的适用性。包裹抗癌药物紫杉醇的DNA适体展示纳米颗粒能够与过表达MUC1的细胞结合并诱导细胞死亡。
DNA-displaying nanoparticles comprised of conjugates of single-stranded DNA (ssDNA) and elastin-like polypeptide (ELP) were developed. ssDNA was enzymatically conjugated to ELPs via a catalytic domain of Porcine Circovirus type 2 replication initiation protein (pRep) fused to ELPs. Nanoparticles were formed upon heating to temperatures above the phase transition temperature due to the hydrophobicity of ELPs and the hydrophilicity of conjugated ssDNA. We demonstrated the applicability of the resultant nanoparticles as drug carriers with tumor-targeting properties by conjugating a DNA aptamer, which is known to bind to Mucin 1 (MUC1), to ELPs. DNA aptamer-displaying nanoparticles encapsulating the anti-cancer drug paclitaxel were able to bind to cells overexpressing MUC1 and induce cell death.