Abstract:
: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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Wang Y,Chen H,Liu Y,Wu J,Zhou P,Wang Y,Li R,Yang X,Zhang Ndoi
10.1016/j.biomaterials.2013.05.081subject
Has Abstractpub_date
2013-09-01 00:00:00pages
7181-90issue
29eissn
0142-9612issn
1878-5905pii
S0142-9612(13)00673-Xjournal_volume
34pub_type
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