Open AccessChemically modified liposomes carrying TRAIL target activated hepatic stellate cells and ameliorate hepatic fibrosis in vitro and in vivo
Author(s) -
Li Qinghua,
Ding Youcheng,
Guo Xinlai,
Luo Shenggen,
Zhuang Huiren,
Zhou JingE,
Xu Nan,
Yan Zhiqiang
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14097
Subject(s) - hepatic stellate cell , in vivo , apoptosis , in vitro , chemistry , hepatic fibrosis , fibrosis , cell , liposome , viability assay , pharmacology , cancer research , pathology , medicine , biology , biochemistry , microbiology and biotechnology
At present, no satisfactory anti‐liver fibrosis drugs have been used clinically due to the poor targeting ability and short half‐life period. This study aimed to explore the effects of a new TRAIL ( TNF ‐related apoptosis‐inducing ligand) preparation that can target aHSC s (activated hepatic stellate cells) on liver fibrosis and explain the possible underlying mechanism. Using our self‐made drug carrier pPB ‐ SSL that specifically targets aHSC s, recombinant human TRAIL (rh TRAIL ) protein was embedded in (named as pPB ‐ SSL ‐ TRAIL ) and applied to treat liver fibrotic mice as well as 3T3 fibroblast cells and aHSC s. Through in vitro and in vivo experiments, we found that, compared with the groups treated with TRAIL (free rh TRAIL ) and SSL ‐ TRAIL (rh TRAIL capsulated within unmodified liposome), the group treated with pPB ‐ SSL ‐ TRAIL nanoparticles showed significantly lower cell viability and higher cell apoptosis in vitro. The targeting delivering system pPB ‐ SSL also significantly enhanced the anti‐fibrotic effect, apoptosis induction and long circulation of rh TRAIL . After the treatment with pPB ‐ SSL ‐ TRAIL , apoptosis of aHSC s was notably increased and hepatic fibrosis in mice was remarkably alleviated. In vitro, pPB ‐ SSL ‐ TRAIL nanoparticles were mainly transported and located on membrane or into cytoplasm, but the particles were distributed mainly in mouse fibrotic liver and most on the cell membrane of aHSC s. In conclusion, rh TRAIL carried by pPB ‐ SSL delivering system has prolonged circulation in blood, be able to target aHSC s specifically, and alleviate fibrosis both in vitro and in vivo. It presents promising prospect in the therapy of liver fibrosis, and it is worthwhile for us to develop it for clinical use.