Although nanotechnology has led to important advances in in vitro diagnostics, the development of nanosensors for in vivo detection remains very challenging. Here, we demonstrated the proof-of-principle of in vivo detection of nucleic acid targets using a promising type of surface-enhanced Raman scattering (SERS) nanosensor implanted in the skin of a large animal model (pig). The in vivo nanosensor used in this study involves the “inverse molecular sentinel” detection scheme using plasmonics-active nanostars, which have tunable absorption bands in the near infrared region of the “tissue optical window”, rendering them efficient as an optical sensing platform for in vivo optical detection. Ex vivo measurements were also performed using human skin grafts to demonstrate the detection of SERS nanosensors through tissue. In this study, a new core–shell nanorattle probe with Raman reporters trapped between the core and shell was utilized as an internal standard system for self-calibration. These results illustrate the usefulness and translational potential of the SERS nanosensor for in vivo biosensing.

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尽管纳米技术已经在体外诊断方面取得了重要进展，但是用于体内检测的纳米传感器的开发仍然非常具有挑战性。在这里，我们证明了使用植入大型动物模型（猪）皮肤中的有前途的表面增强拉曼散射（SERS）纳米传感器类型，在体内检测核酸靶标的原理证明。在体内在本研究中使用纳米传感器包括使用等离子体活性纳米星，其具有在“组织光学窗”的近红外区域的可调谐吸收带的“逆分子前哨”检测方案，使它们有效地作为一个光学感测平台体内光学检测。还使用人体皮肤移植物进行了离体测量，以证明可以通过组织检测SERS纳米传感器。在这项研究中，一种新型的核-壳纳米ttle子探针，其拉曼报告分子被困在核和壳之间，被用作自校准的内标系统。这些结果说明了SERS纳米传感器在体内生物传感中的有用性和翻译潜力。

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