期刊
NANO LETTERS
卷 19, 期 2, 页码 937-947出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b04179
关键词
CuS nanoparticles; activatable probe; molecular imaging; photothermal therapy; gastric tumor
类别
资金
- National Key R&D Program of China [2017YFA0701301]
- National Natural Science Foundation of China [81671751, 81871410, 21632008, 21775071]
- Natural Science Foundation of Jiangsu Province [BK20150567, BK20171118]
- Social Development Foundation of Jiangsu Province [BE2015605]
- Medical Science and technology development Foundation Nanjing [JQX16022]
- Jiangsu Province Key Medical Young Talents, 13th Five-Year Health Promotion Project Of Jiangsu Province [QNRC2016041]
- Scientific Research Foundation of Graduate School of Nanjing University [2017CL05]
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 r(1) relaxivity (similar to 60.0 mM(-1) s(-1) per Gd3+ at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (similar to 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, similar to 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 (similar to 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., alpha(v)beta(3) and MMP-2) and dual modality imaging (i.e., MM and NIR fluorescence) to design tumor-targeting and activatable nanoprobes with improved selectivity for cancer theranostics in vivo.
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