期刊
BIOMATERIALS
卷 182, 期 -, 页码 269-278出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.08.026
关键词
Chimeric peptide; MMP-2; Transformation; MRI enhancement; Photodynamic therapy
资金
- National Natural Science Foundation of China [21778020, 51603080]
- Fundamental Research Funds for the Central Universities [2662015QD026]
- Sci-tech Innovation Foundation of Huazhong Agriculture University [2662017PY042, 2662018PY024]
Despite the great success in clinical magnetic resonance imaging (MRI), Gd3+-based contrast agents still suffer from low proton relaxation efficiency, rapid metabolic clearance as well as poor sensitivity. In this work, we designed a matrix metalloproteinase-2 (MMP-2) responsive chimeric peptide for dual-stage-amplified MRI and precise photodynamic therapy. Both in vitro and in vivo studies indicated that this chimeric peptide could selfassembly into spherical nanoparticles at physiological condition with r(1) value of 28.17 mM(-1) s(-1). Meanwhile, the spherical shape endowed chimeric peptide with efficient tumor accumulation via enhanced penetration and retention (EPR) effect. Importantly, the overexpressed MMP-2 in tumor region could specifically hydrolyze chimeric peptide, leading to sphere-to-fiber transformation. This transformation enhanced both the tumor accumulation and the relaxivity of contrast agent. Consequently, the r(1) value was remarkably elevated to 51.52 mM(-1) s(-1) , which guided precise photodynamic therapy. This tumor microenvironment-triggered transformable strategy should show great potential for tumor-targeted imaging and phototherapy.
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