NPs) with unique optical properties have emerged as one of the most exciting tools in nanomedicine, capable of achieving multiple tasks such as optical imaging, [2] targeted chemotherapy, [3] and localized photothermal therapy (PTT), [4][5][6] for efficient tumor theragnostics and preventing tumor recurrence. Prior to the therapy, the solid tumor can be spatially visualized by NP-based imaging techniques for precise diagnosis. Among various NPenhanced imaging technologies, surfaceenhanced Raman spectroscopy (SERS) has exhibited great potential for ultrasensitive biological imaging with advantages of low-cost, non-ionizing excitation light, the unique vibrational spectrum, ultra-narrow spectral line-width, high resistance to photo bleaching, and high signal-to-noise ratio. [7,8] Especially, it has been employed for tracking the biodistribution of injected NPs in vivo systems. For instance, Campbell et al. used Raman imaging to evaluate the biodistribution and clearance kinetics of plamonic NPs together with other techniques, including positron emission tomography (microPET), hyperspectral imaging, and inductively coupled plasma mass spectrometry (ICP-MS) over 48 h post-ingestion, [9] suggesting the reliability of translating high-sensitivity Raman contrast imaging into clinical practice. Therefore, there is high demand for developing strong NP-constructed SERS tags that show great prospects for effective optical guidance of tumor identification and imaging.
Surface-enhanced Raman scattering (SERS) imaging has emerged as a promising tool for guided cancer diagnosis and synergistic therapies, such as combined chemotherapy and photothermal therapy (chemo-PTT). Yet, existing therapeutic agents often suffer from low SERS sensitivity, insufficient photothermal conversion, or/and limited drug loading capacity. Herein, a multifunctional theragnostic nanoplatform consisting of mesoporous silicacoated gold nanostar with a cyclic Arg-Gly-Asp (RGD)-coated gold nanocluster shell (named RGD-pAS@AuNC) is reported that exhibits multiple "hot spots" for pronouncedly enhanced SERS signals and improved nearinfrared (NIR)-induced photothermal conversion efficiency (85.5%), with a large capacity for high doxorubicin (DOX) loading efficiency (34.1%, named RGD/DOX-pAS@AuNC) and effective NIR-triggered DOX release. This nanoplatform shows excellent performance in xenograft tumor model of HeLa cell targeting, negligible cytotoxicity, and good stability both in vitro and in vivo. By SERS imaging, the optimal temporal distribution of injected RGD/ DOX-pAS@AuNCs at the tumor site is identified for NIR-triggered local chemo-PTT toward the tumor, achieving ultraeffective therapy in tumor cells and tumor-bearing mouse model with 5 min of NIR irradiation (0.5 W cm −2 ). This work offers a promising approach to employing SERS imaging for effective noninvasive tumor treatment by on-site triggered chemo-PTT.