Open AccessPreparation of T‑2 toxin‑containing pH‑sensitive liposome and its antitumor activity
Author(s) -
Yuan Dong,
Guixian Meng,
Jialong Guo,
Moli Yin,
Huijing Xu,
Yujie Li,
Jie Zhu,
Wenhe Zhu,
Mingguang Li,
Yan Li,
Huiyan Wang
Publication year - 2020
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2020.11531
Subject(s) - phosphatidylcholine , toxin , liposome , chemistry , phospholipid , chromatography , bromide , tris , phosphate , nuclear chemistry , cytotoxicity , biochemistry , in vitro , organic chemistry , membrane
T‑2 toxin is a type A trichothecene mycotoxin. In order to reduce the side effects of T‑2 toxin and increase the tumor targeting ability, a pH‑sensitive liposome of T‑2 toxin (LP‑pHS‑T2) was prepared and characterized in the present study. The cytotoxicity of LP‑pHS‑T2 on A549, Hep‑G2, MKN‑45, K562 and L929 cell lines was tested by 3‑(4,5‑dimethylthiazolyl‑2)‑2,5‑diphenyltetrazolium bromide assay, with T‑2 toxin as the control. The apoptotic and migratory effects of LP‑pHS‑T2 on Hep‑G2 cells were investigated. The preparation process of LP‑pHS‑T2 involved the following parameters: Dipalmitoyl phosphatidylcholine: dioleoylphosphatidylethanolamine, 1:2; total phospholipid concentration, 20 mg/ml; phospholipid:cholesterol, 3:1; 4‑(2‑hydroxyethyl)‑1‑piperazineethanesulfonic acid buffer (pH 7.4), 10 ml; drug:lipid ratio, 2:1; followed by ultrasound for 10 min and extrusion. The encapsulation efficiency reached 95±2.43%. The average particle size of LP‑pHS‑T2 after extrusion was 100 nm; transmission electron microscopy showed that the shape of LP‑pHS‑T2 was round or oval and of uniform size. The release profile demonstrated a two‑phase downward trend, with fast leakage of T‑2 toxin in the first 6 h (~20% released), followed by sustained release up to 48 h (~46% released). From 48‑72 h, the leakage rate increased (~76% released), until reaching a minimum at 72 h. When LP‑pHS‑T2 was immersed in 0.2 mol/l disodium phosphate‑sodium dihydrogen phosphate buffers (pH 6.5), the release speed was significantly increased and the release rate reached 91.2%, demonstrating strong pH sensitivity. Overall, antitumor tests showed that LP‑pHS‑T2 could promote the apoptosis and inhibit the migration of Hep‑G2 cells. The present study provided a new approach for the development of T‑2 toxin‑based anti‑cancer drugs.