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In Vitro and In Vivo Evaluation of SP94 Modified Liposomes Loaded with N-14NCTDA, a Norcantharimide Derivative for Hepatocellular Carcinoma-Targeting

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Abstract

The purpose of this research is to develop a liposomal drug delivery system, which can selectively target hepatocellular carcinoma (HCC) to deliver the antitumor agent N-14NCTDA, a C14 alkyl chain norcantharimide derivative of norcantharidin. N-14NCTDA-loaded liposomes were successfully prepared by lipid membrane hydration and extrusion methods. SP94, a targeting peptide for HCC cells, was attached to the liposomes loaded with N-14NCTDA by the post-insertion method to obtain SP94 modified liposomes (SP94-LPs). SP94-LPs had a significant cytotoxicity against Hep G2 cells with the IC50 of 15.395 ± 0.89 μg/mL, which is lower than that of NCTD-S (IC50 = 20.863 ± 0.56 μg/mL) and GAL-LPs (IC50 = 24.589 ± 1.02 μg/mL). Compared with conventional liposomes (Con-LPs), SP94-LPs showed greater cellular uptake in Hep G2 cells. Likewise, significant tumor suppression was achieved in H22 tumor-bearing mice which were treated with SP94-LPs. The tumor inhibition rate (IRw) of SP94-LPs was 82 ± 0.98%, obviously higher than that of GAL-LPs (69 ± 1.39%), Con-LPs (60 ± 2.78%), and NCTD-S (51 ± 3.67%). SP94-LPs exhibited a significant hepatocellular carcinoma-targeting activity in vitro and in vivo, which will provide a new alternative for hepatocellular carcinoma treatment in future.

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Funding

This study received financial support from the Liaoning Province Natural Science Fund Project (No.20180551031), and Overseas returnees start-up fund of Shenyang Pharmaceutical University (No. GGJJ2018102).

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Author notes

  1. Ying Jiang and Xiaolin Liu contributed equally.

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People’s Republic of China

    Ying Jiang, Xinyi Tan, Ye Hou, Wanxiao Sun, Jingxin Gou, Haibing He, Yu Zhang & Xing Tang

  2. Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China

    Xiaolin Liu

  3. School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People’s Republic of China

    Tian Yin

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  1. Ying Jiang
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  2. Xiaolin Liu
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  4. Ye Hou
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Contributions

YJ and XLL performed all experiments and wrote the manuscript. YXT contributed to data acquisition and analysis. Others contributed to data acquisition. The corresponding author YZ contributed to conception, design, data interpretation, and critically revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yu Zhang.

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Jiang, Y., Liu, X., Tan, X. et al. In Vitro and In Vivo Evaluation of SP94 Modified Liposomes Loaded with N-14NCTDA, a Norcantharimide Derivative for Hepatocellular Carcinoma-Targeting. AAPS PharmSciTech 21, 277 (2020). https://doi.org/10.1208/s12249-020-01829-3

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