Fan Quli, Cheng Kai, Hu Xiang, Ma Xiaowei, Zhang Ruiping, Yang Min, Lu Xiaomei, Xing Lei, Huang Wei, Gambhir Sanjiv Sam, Cheng Zhen
Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, School of Medicine, Stanford University , Stanford, California 94305-5484, United States.
J Am Chem Soc. 2014 Oct 29;136(43):15185-94. doi: 10.1021/ja505412p. Epub 2014 Oct 16.
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, (64)Cu(2+), Fe(3+)). 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.
开发具有集成不同模态的多功能且易于制备的纳米平台对于分子成像极具挑战性。在此，我们报告了将一个重要的分子靶点——黑色素成功转化为一种新型的多模态成像纳米平台。黑色素在黑色素瘤中大量表达，因此一直作为黑色素瘤成像的靶点被积极研究。在我们的工作中，基于超小（<10 nm）水溶性黑色素纳米颗粒（MNP）开发了多功能生物聚合物纳米平台，该平台展现出独特的光声特性以及与金属离子（例如，(64)Cu(2+)、Fe(3+)）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基团或使用活性基团进行化学修饰，以将不同的造影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极大地简化构建过程。我们进一步将αvβ3整合素、环化c(RGDfC)肽偶联到MNPs上，由于其靶向特性与增强的通透性和滞留（EPR）效应相结合，从而实现U87MG肿瘤的富集。MNPs的多模态特性证明了具有多功能的内源性材料作为分子治疗诊断学和临床转化纳米平台的巨大潜力。
