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Studies of anticancer activity in vivo and in vitro behaviors of liposomes encapsulated iridium(III) complex.
- Source :
-
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry [J Biol Inorg Chem] 2021 Feb; Vol. 26 (1), pp. 109-122. Date of Electronic Publication: 2021 Jan 21. - Publication Year :
- 2021
-
Abstract
- Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq) <subscript>2</subscript> (DQTT)](PF <subscript>6</subscript> ) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca <superscript>2+</superscript> . Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents toxicity
Apoptosis drug effects
Calcium metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Coordination Complexes chemistry
Coordination Complexes toxicity
Drug Carriers toxicity
Drug Liberation
Hemolysis drug effects
Iridium chemistry
Iridium toxicity
Liposomes toxicity
Membrane Potential, Mitochondrial drug effects
Mice
Mitochondria drug effects
NIH 3T3 Cells
Neoplasms pathology
Reactive Oxygen Species metabolism
Signal Transduction
Xenograft Model Antitumor Assays
Antineoplastic Agents therapeutic use
Coordination Complexes therapeutic use
Drug Carriers chemistry
Liposomes chemistry
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1327
- Volume :
- 26
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33475857
- Full Text :
- https://doi.org/10.1007/s00775-020-01841-9