期刊
BIOMATERIALS
卷 34, 期 29, 页码 7181-7190出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.05.081
关键词
Pullulan; Nanoparticle carrier; Targeting; Combination therapy
资金
- 973 program [2012CBA01305, 2011CB933100]
- National Science Fund for Distinguished Young Scholars [81125019]
- National Natural Science Foundation of China [30900303]
This study designs a pH-sensitive nanoparticle carrier of methotrexate (MTX) and combretastatin A4 (CA4) based on pullulan for the combination therapy against hepatocellular carcinoma (HCC). Briefly, N-urocanyl pullulan (URPA) with the degree of substitution (DS) of 5.2% was synthesized and then conjugated with MTX to form MTX-URPA, in which MTX content was 17.8%. MTX-URPA nanoparticles prepared by the dialysis method had spherical shape and the mean size of 187.1 nm, and showed high affinity for HepG2 cells. CA4 was successfully loaded into MTX-URPA nanoparticles and exhibited pH-sensitive in vitro release property. After intravenous injection to PLC/PRF/5-bearing nude mice, CA4 loaded MTX-URPA (CA4/MTX-URPA) nanoparticles achieved the enhanced antitumor and anti-angiogenic effects, the prolonged circulation time in blood, and the increased distributions both in the liver and the tumor. In conclusion, this drug carrier system has significant liver-targeting property and exhibits advantages for the combination therapy against hepatocellular carcinoma. (C) 2013 Elsevier Ltd. All rights reserved.
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