Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides
Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides
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DOI：
10.1002/adma.201705383
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发表时间：
2018-02
影响因子：
29.4
通讯作者：
Xi Yu;Xingchun Gou;Peng Wu;Liang Han;Daofeng Tian;F. Du;Zeming Chen;Fuyao Liu;Gang Deng;A. Chen;Chao Ma;Jun Liu;S. Hashmi;Xing Guo;Xiaolong Wang;Haitian Zhao;Xinran Liu;Xudong Zhu;K. Sheth;Qianxue Chen;L. Fan;Jiangbing Zhou
中科院分区：
文献类型：
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作者：
Xi Yu;Xingchun Gou;Peng Wu;Liang Han;Daofeng Tian;F. Du;Zeming Chen;Fuyao Liu;Gang Deng;A. Chen;Chao Ma;Jun Liu;S. Hashmi;Xing Guo;Xiaolong Wang;Haitian Zhao;Xinran Liu;Xudong Zhu;K. Sheth;Qianxue Chen;L. Fan;Jiangbing Zhou
治疗性肽的临床翻译，特别是那些需要穿透细胞膜或溶细胞的治疗性肽的临床翻译，是一个主要的挑战。描述了一种基于互补机制的新方法，该方法已广泛用于DNA或RNA纳米颗粒的指导合成，用于从头设计用于靶向递送治疗肽的可活化蛋白质纳米颗粒（APNP）。APNP通过基于成对卷曲螺旋二聚化的三个独立多肽的自组装形成。它们能够在血液中长时间循环，并且可以被设计为针对疾病。将待递送的肽掺入APNP中并通过局部富集的蛋白酶释放到疾病微环境中。证明APNP介导NR2B9c（一种在细胞穿透后起作用的神经保护肽）和蜂毒肽（一种扰乱脂质双层的细胞溶解肽）的有效递送，分别用于有效治疗中风和癌症。由于其强大的性能，简单的设计和经济的成本，APNP具有很大的潜力，作为一个通用的平台，用于控制输送的治疗肽。
Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self‐assembly of three independent polypeptides based on pairwise coiled‐coil dimerization. They are capable of long circulation in the blood and can be engineered to target diseases. Peptides to be delivered are incorporated into APNPs and released into the disease microenvironment by locally enriched proteases. It is demonstrated that APNPs mediate efficient delivery of NR2B9c, a neuroprotective peptide that functions after cell penetration, and melittin, a cytolytic peptide that perturbs the lipid bilayer, for effective treatment of stroke and cancer, respectively. Due to their robust properties, simple design, and economic costs, APNPs have great potential to serve as a versatile platform for controlled delivery of therapeutic peptides.