摘要
A eukaryotic cell contains thousands of proteins that regulate its cellular function; delivering functional proteins into cells to rectify cellular functions holds great promise for treatment of various diseases, especially cancers. In this context, ribonuclease (RNase), an enzyme that breaks down ribonucleic acid (RNA), has great potential for cancer therapy. However, its therapeutic application is hampered by poor intracellular delivery efficiency and inhibition by ubiquitous intracellular RNase inhibitors. In this work, by designing and synthesizing RNase nano-conjugates by in situ atom transfer radical polymerization (ATRP), we demonstrate a simple solution to address both challenges. Compared with native RNase, nano-conjugates exhibit significantly enhanced intracellular delivery efficiency, inhibitor resistance, and a near five-fold increase in cytotoxicity. This work provides a novel platform for delivery of therapeutic proteins for cancer therapy and other applications.
一个真核细胞的房间包含调整它的细胞的功能的几千蛋白质;交付功能的蛋白质进房间修正细胞的功能为各种各样的疾病的治疗保持大诺言,特别癌症。在这上下文, ribonuclease (RNase ) ,毁坏核糖核酸酸(RNA ) 的酶,为癌症有大潜力治疗。然而,它的治疗学的申请被无所不在的细胞内部的 RNase 禁止者被差的细胞内部的交货效率和抑制妨碍。在这工作,由设计和综合 RNase nano 结合由在 situ 原子转移基聚合(ATRP ) ,我们表明简单溶液到地址两挑战。与本国的 RNase 相比, nano 结合展览显著地提高了细胞内部的交货效率,禁止者抵抗,和 cytotoxicity 的近五倍的增加。这个工作为癌症治疗和另外的应用为治疗学的蛋白质的交货提供一个新奇平台。