Preparation of T‑2 toxin‑containing pH‑sensitive liposome and its antitumor activity

Abstract

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.

Desmethyl SuFEx-IT: SO2F2-Free Synthesis and Evaluation as a Fluorosulfurylating Agent

“…Therefore, our interest shifted to desmethyl SuFEx-IT ( 11 ), which should represent a more accessible alternative to SuFExIT. Although the preparation of 11 has been described in the patent literature, 13 neither its suitability as a FO 2 S-transfer agent nor its storage stability have been evaluated so far. In addition, the reported procedure for preparation of desmethyl SuFEx-IT is essentially the same as for the production SuFEx-IT and thus suffers from the same drawbacks.…”