期刊
BIOMATERIALS
卷 51, 期 -, 页码 30-42出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.01.063
关键词
Radiotherapy; Targeted nanodrug delivery; Mesoporous silica nanoparticles; Apoptosis
资金
- National High Technology Research and Development Program of China [SS2014AA020538]
- Science Foundation for Distinguished Young Scholars of Guangdong Province [S2013050014667]
- Natural Science Foundation of China [21271002, 21371076, 21201082]
- Natural Science Foundation of Guangdong Province [S2012040006919]
- Foundation for High-level Talents in Higher Education of Guangdong
- Research Fund for the Doctoral Program of Higher Education of China [20114401110004]
- Shenzhen Basic Research Grant [JCYJ20130401152508660]
- YangFan Innovative & Entepreneurial Research Team Project [201312H05]
Radioresistance and limitation of irradiative dosage usually lead to failure in depletion of hypoxic tumors. Herein we developed multifunctional mesoporous silica nanoparticles (MSNs) as a carrier of a novel anticancer selenoamino acid (selenocystine, SeC), to achieve synergistic chemo-/radiotherapy. This multifunctional nanosystem effectively sensitizes cancer cells to X-ray radiotherapy. Conjugation of TAT cell penetrating peptide and transferrin to the surface of MSNs significantly enhances its internalization in cancer cells through receptor-mediated endocytosis. SeC@MSNs-Tf/TAT significantly enhanced X-ray-induced growth inhibition in cervical cancer cells by induction of apoptosis, mainly through death receptor-mediated extrinsic apoptotic pathway. Upon radiation, SeC@MSNs-Tf/TAT promoted intracellular ROS overproduction, which induced apoptotic cell death by affecting p53, ART and MAPKs pathways. Furthermore, SeC@MSNs-Tf/TAT also significantly inhibited HeLa tumor growth in nude mice model through suppression of cell proliferation and induction of apoptosis. In vivo toxicity of the SeC@MSNs-Tf/TAT nanoparticles was investigated using the mouse model. The results of histological analysis revealed that, the nanoparticles did not show any obvious damage to these major organs under the experimental conditions, including heart, liver, spleen, lung and kidney. Taken together, this study demonstrates an effective and safe strategy for cancer-targeted chemo-/radiotherapy of human cancers. (C) 2015 Elsevier Ltd. All rights reserved.
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