期刊
JOURNAL OF CONTROLLED RELEASE
卷 224, 期 -, 页码 217-228出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2015.12.050
关键词
Theranostic nanoparticles; Imaging-guided therapy; iRGD; Indocyanine green; Phototherapy
资金
- National Key Basic Research Program of China (973 Program) [2015CB755500, 2014CB744502, 2013CB733800]
- National Natural Science Foundation of China [81371563, 81360482, 11325420, 81401435, 81571674, 61327001]
- Natural Science Foundation of Guangdong Province [2014A030313341]
- National High Technology Research and Development Program of China (863 Program) [2014AA020503]
Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to alpha v beta 3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG(2000)-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD-ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealedmuchmore apoptotic cells, confirming the advantageous anti-tumor effect of iRGD-ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy. (C) 2015 Published by Elsevier B.V.
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