Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.

Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.
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将生物标志物转移到分子探针中:黑色素纳米颗粒作为多模态成像的天然活性平台

DOI:
10.1021/ja505412p
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发表时间:
2014-10-29
影响因子:
15
通讯作者:
Cheng Z
Cheng Z
中科院分区:
化学1区
文献类型:
--
作者:
Fan Q;Cheng K;Hu X;Ma X;Zhang R;Yang M;Lu X;Xing L;Huang W;Gambhir SS;Cheng Z

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开发具有集成不同模式的多功能且易于制备的纳米平台对于分子成像来说是极具挑战性的。在这里,我们报告了将重要的分子靶标黑色素成功转移到新型多模态成像纳米平台中。黑色素在黑色素瘤中大量表达,因此作为黑色素瘤成像的靶点已被积极研究。在我们的工作中,开发了基于超小(<10 nm)水溶性黑色素纳米颗粒(MNP)的多功能生物聚合物纳米平台,并表现出独特的光声特性和与金属离子(例如,64Cu2+、Fe3+)的天然结合能力。因此,MNP不仅可以作为光声造影剂,还可以作为正电子发射断层扫描(PET)和磁共振成像(MRI)的纳米平台。传统的被动纳米平台需要复杂且耗时的过程来预先构建报告部分或使用活性基团进行化学修饰以将不同的对比特性整合到一个实体中。相比之下,利用功能性生物标志物黑色素可以大大简化构建过程。我们进一步将 αvβ3 整合素、环 c(RGDfC) 肽与 MNP 结合,由于其靶向特性与增强渗透性和保留 (EPR) 效应相结合,允许 U87MG 肿瘤积累。 MNP 的多峰特性证明了具有多功能的内源性材料作为分子治疗诊断和临床转化纳米平台的巨大潜力。
Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (<10 nm) water-soluble melanin nanoparticle (MNP) was developed and showed unique photoacoustic property and natural binding ability with metal ions (for example, 64Cu2+, Fe3+). Therefore, MNP can serve not only as a photoacoustic contrast agent, but also as a nanoplatform for positron emission tomography (PET) and magnetic resonance imaging (MRI). Traditional passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated αvβ3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.