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

Authors Zhang CG, Zhu QL, Zhou Y, Liu Y, Chen WL, Yuan ZQ, Yang SD, Zhou XF, Zhu AJ, Zhang XN, Jin Y

Received 27 December 2013

Accepted for publication 15 February 2014

Published 13 June 2014 Volume 2014:9(1) Pages 2919—2932

DOI https://doi.org/10.2147/IJN.S59799

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Chun-ge Zhang,*,1 Qiao-ling Zhu,*,1 Yi Zhou,*,1,2 Yang Liu,1 Wei-liang Chen,1 Zhi-Qiang Yuan,1 Shu-di Yang,1 Xiao-feng Zhou,3,4 Ai-jun Zhu,1 Xue-nong Zhang,*,1 Yong Jin*,5

1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 2The Children's Hospital of Wuxi People's Hospital, Nanjing Medical University, Wuxi, 3College of Radiological Medicine and Protection, Soochow University, Suzhou, 4Changshu Hospital of Traditional Chinese Medicine, Changshu, 5Invasive Technology Department, The Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
  
*These authors contributed equally to this work

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: liver cancer, targeting efficacy, antitumor activity

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