Pal Suchetan, Harmsen Stefan, Oseledchyk Anton, Hsu Hsiao-Ting, Kircher Moritz F
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
Adv Funct Mater. 2017 Aug 25;27(32). doi: 10.1002/adfm.201606632. Epub 2017 Jul 6.
Recently, surface-enhanced Raman scattering (SERS) nanoprobes (NPs) have shown promise in the field of cancer imaging due to their unparalleled signal specificity and high sensitivity. Here we report the development of a DNA aptamer targeted SERS NP. Recently, aptamers are being investigated as a viable alternative to more traditional antibody targeting due to their low immunogenicity and low cost of production. We developed a strategy to functionalize SERS NPs with DNA aptamers, which target Mucin1 (MUC1) in human breast cancer (BC). Thorough in vitro characterization studies demonstrated excellent serum stability and specific binding of the targeted NPs to MUC1. In order to test their targeting capability, we co-injected MUC1-targeted SERS NPs, and as controls non-targeted and blocked MUC1-targeted SERS NPs in BC xenograft mouse models. A two-tumor mouse model with differential expression of MUC1 (MDA-MB-468 and MDA-MB-453) was used to control for active versus passive targeting in the same animals. The results showed that the targeted SERS NPs home to the tumors via active targeting of MUC1, with low levels of passive targeting. We expect this strategy to be an advantageous alternative to antibody-based targeting and useful for targeted imaging of tumor extent, progression, and therapeutic response.
最近，表面增强拉曼散射（SERS）纳米探针（NPs）因其无与伦比的信号特异性和高灵敏度，在癌症成像领域展现出了应用前景。在此，我们报告一种靶向DNA适配体的SERS NP的研发情况。近来，由于免疫原性低且生产成本低，适配体正被作为一种可行的替代方案，用于替代更为传统的抗体靶向方法。我们开发了一种用DNA适配体使SERS NPs功能化的策略，该适配体靶向人类乳腺癌（BC）中的粘蛋白1（MUC1）。全面的体外表征研究证明了靶向NPs具有出色的血清稳定性以及与MUC1的特异性结合。为了测试它们的靶向能力，我们在BC异种移植小鼠模型中共注射了靶向MUC1的SERS NPs，以及作为对照的非靶向和封闭的靶向MUC1的SERS NPs。利用具有MUC1差异表达的双肿瘤小鼠模型（MDA-MB-468和MDA-MB-453）来控制同一动物中的主动靶向与被动靶向。结果表明，靶向SERS NPs通过对MUC1的主动靶向作用归巢至肿瘤部位，被动靶向水平较低。我们期望这种策略能够成为基于抗体靶向的一种优势替代方法，并有助于对肿瘤范围、进展和治疗反应进行靶向成像。
