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Int J Nanomedicine. 2014 Jun 13;9:2919-32. doi: 10.2147/IJN.S59799. eCollection 2014.

N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors.

Author information

  • 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
  • 2Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China ; The Children's Hospital of Wuxi People's Hospital, Nanjing Medical University, Wuxi, People's Republic of China.
  • 3College of Radiological Medicine and Protection, Soochow University, Suzhou, People's Republic of China ; Changshu Hospital of Traditional Chinese Medicine, Changshu, People's Republic of China.
  • 4Invasive Technology Department, The Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

Abstract

N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor.

KEYWORDS:

antitumor activity; liver cancer; targeting efficacy

PMID:
24966673
[PubMed - indexed for MEDLINE]
PMCID:
PMC4063822
Free PMC Article
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