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Nanomedicine. 2018 Aug;14(6):1949-1961. doi: 10.1016/j.nano.2017.09.012. Epub 2017 Oct 16.

Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody-conjugated immunoliposomes.

Author information

1
Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
2
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
3
Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai, China; Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
4
Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address: jiang_beige@aliyun.com.
5
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address: weilixin_smmu@163.com.
6
Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai, China; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. Electronic address: gaojie@smmu.edu.cn.
7
Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address: ehphwp@126.com.

Abstract

HAb18G/CD147, an important marker in the progression of hepatocellular carcinoma (HCC), is highly expressed on the surface of HCC cells. To increase the therapeutic efficacy of Doxil (PEGylated liposomal doxorubicin) against HCC, we constructed CD147-targeted doxorubicin-loaded immunoliposomes (Anti-CD147 ILs-DOX) by conjugating F(ab')2 of a CD147-specific monoclonal antibody to DSPE-PEG-MAL, and then inserted the antibody-conjugated polymer to Doxil. Anti-CD147 ILs-DOX delivered DOX to CD147-overexpressing HCC cells specifically and efficiently in vitro and in vivo, resulting in enhanced therapeutic effects than non-targeted controls. Strikingly, Anti-CD147 ILs-DOX reduced the CD133-positive fraction of HCC cells, suggesting its potential in reducing the number of HCC stem cells. Pharmacokinetic and biodistribution studies of Anti-CD147 ILs-DOX confirmed its long circulation time and efficient accumulation in tumors. The superior antitumor effects of Anti-CD147 ILs-DOX than other treatments were demonstrated in both HCC cells and patient-derived HCC xenograft models. Anti-CD147 ILs-DOX represent a novel approach for targeted HCC therapy.

KEYWORDS:

Antibody; CD147; Doxorubicin; Hepatocellular carcinoma; Liposomes

PMID:
29045824
DOI:
10.1016/j.nano.2017.09.012
[Indexed for MEDLINE]

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