A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties
A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties
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一种源自镧系元素肽的类细菌纳米治疗剂，具有高肿瘤靶向、成像和杀伤特性
DOI：
10.1016/j.biomaterials.2019.03.026
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发表时间：
2019-06-01
期刊：
影响因子：
14
通讯作者：
Ma, Peter X.
中科院分区：
文献类型：
--
作者：
He, Wangxiao;Yan, Jin;Ma, Peter X.
由生物活性肽形成的纳米结构作为一类新型的人类癌症治疗剂在临床肿瘤学中提供了令人兴奋的前景。然而，尽管它们具有治疗潜力，但基于肽的纳米药物通常由于低货物装载效率、差的肿瘤细胞靶向特异性和肿瘤组织中有限的药物积累而在体内无效。在这里，我们描述的设计，通过组装的p53激活肽称为PMI，功能化的PEG和荧光镧系元素氟氧化物纳米晶体，一种新的nanotheranostic形状的柔性棒。这种镧系元素肽纳米棒或仿生性质的LProd表现出显着增强的肿瘤靶向和成像性能相比，其球形对应物。重要的是，LProd通过MDM 2/MDMX拮抗作用激活肿瘤抑制蛋白p53，有效抑制人类结肠癌小鼠模型中的肿瘤生长，同时保持高度有利的生物安全性。我们的数据表明，LProd作为一种多功能治疗诊断平台，非常适合用于肿瘤特异性肽药物递送和实时疾病跟踪，从而广泛影响抗肿瘤肽的临床开发。
Nanostructures formed with bioactive peptides offer an exciting prospect in clinical oncology as a novel class of therapeutic agents for human cancers. Despite their therapeutic potential, however, peptide-based nanomedicines are often inefficacious in vivo due to low cargo-loading efficiency, poor tumor cell-targeting specificity and limited drug accumulation in tumor tissues. Here, we describe the design, via assembly of a p53-activating peptide termed PMI, functionalized PEG and fluorescent lanthanide oxyfluoride nanocrystals, of a novel nanotheranostic shaped in flexible rods. This lanthanide-peptide nanorod or LProd of bionic nature exhibited significantly enhanced tumor-targeting and -imaging properties compared to its spherical counterpart. Importantly, LProd potently inhibited tumor growth in a mouse model of human colon cancer through activating tumor suppressor protein p53 via MDM2/MDMX antagonism, while maintaining a highly favorable biosafety profile. Our data demonstrate that LProd as a multifunctional theranostic platform is ideally suited for tumor specific peptide drug delivery with real-time disease tracking, thereby broadly impacting clinical development of antitumor peptides.