期刊
BIOMATERIALS
卷 35, 期 3, 页码 983-992出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.09.062
关键词
Nanoparticles; TNP-470; Antiangiogenesis; Ovarian cancer; Antitumor efficiency
资金
- National Natural Science Foundation of China [81101738, 81072138, 81272568]
- Science and Technology Commission of Shanghai Municipality [11nm0503000, 11DZ2211002, 1052nm04800]
- International Cooperation Project from Science and Technology Commission of Shanghai [13430722200]
- Scientific Research Innovation Program from the Shanghai Municipal Education Commission [14YZ029]
- Scientific Project of Shanghai Municipal Health Bureau [20114168]
- Medical-Engineering Joint Funds of Shanghai Jiao Tong University [YG2011MS53]
- Fund of Shanghai Jiao Tong University School of Medicine [12XJ10079]
Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol) poly (lactic acid) (PEG PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG PLA and mPEG PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative zeta-potential (-14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
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