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Magnetic Semiconductor Gd-Doping CuS Nanoparticles as Activatable Nanoprobes for Bimodal Imaging and Targeted Photothermal Therapy of Gastric Tumors

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journal contribution
posted on 28.01.2019, 00:00 by Hua Shi, Yidan Sun, Runqi Yan, Shunli Liu, Li Zhu, Song Liu, Yuzhang Feng, Peng Wang, Jian He, Zhengyang Zhou, Deju Ye
Targeted delivery of enzyme-activatable probes into cancer cells to facilitate accurate imaging and on-demand photothermal therapy (PTT) of cancers with high spatiotemporal precision promises to advance cancer diagnosis and therapy. Here, we report a tumor-targeted and matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed by covalent modification of Gd-doping CuS micellar nanoparticles with cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays a high r1 relaxivity (∼60.0 mM–1 s–1 per Gd3+ at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold) in response to MMP-2, allowing high-spatial-resolution magnetic resonance imaging (MRI) and low-background fluorescence imaging of gastric tumors as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN has a high photothermal conversion efficiency (PCE, ∼70.1%) under 808 nm laser irradiation, endowing it with the ability to efficiently generate heat to kill tumor cells. We demonstrate that T-MAN can accumulate preferentially in gastric tumors (∼23.4% ID%/g at 12 h) after intravenous injection into mice, creating opportunities for fluorescence/MR bimodal imaging-guided PTT of subcutaneous and metastatic gastric tumors. For the first time, accurate detection and laser irradiation-initiated photothermal ablation of orthotopic gastric tumors in intraoperative mice was also achieved. This study highlights the versatility of using a combination of dual biomarker recognition (i.e., αvβ3 and MMP-2) and dual modality imaging (i.e., MRI and NIR fluorescence) to design tumor-targeting and activatable nanoprobes with improved selectivity for cancer theranostics in vivo.