title: The in vitro and in vivo anti-tumor effects of MTX-Fe3O 4-PLLA-PEG-PLLA microspheres prepared by suspension-enhanced dispersion by supercritical CO2.
abstract: The in vitro and in vivo anti-tumor efficacy of methotrexate-loaded Fe3O4-poly-L-lactide-poly(ethylene glycol)-poly-L-lactide magnetic composite microspheres (MTX-Fe3O4-PLLA-PEG-PLLA MCMs, MMCMs), which were produced by co-precipitation (C) and microencapsulation (M) in a supercritical process, was evaluated at various levels: cellular, molecular, and integrated. The results at the cellular level indicate that MMCMs (M) show a better anti-proliferation activity than raw MTX and could induce morphological changes of cells undergoing apoptosis. At the molecular level, MMCMs (M) lead to a significantly higher relative mRNA expression of bax/bcl-2 and caspase-3 than MMCMs (C) at 10 μg mL(-1) (P<0.01); and the pro-caspase-3 protein expression measured by Western blot analysis also demonstrates that MMCMs (M) can effectively activate pro-caspase-3. At the integrated level, mice bearing a sarcoma-180 tumor are used; in vivo anti-tumor activity tests reveal that MMCMs (M) with magnetic induction display a much higher tumor suppression rate and lower toxicity than raw MTX. Pharmacokinetic studies show that MMCMs (M) with magnetic induction significantly increase the accumulation of MTX in the tumor tissue compared with the other treatments. These results suggest that the MMCMs (M) prepared by the SpEDS process have great potential to play a positive role in the magnetic targeted therapy field.
authors.affiliation: College of Chemical Engineering, Huaqiao University, Xiamen, 361021, China, azchen@hqu.edu.cn.
authors.forename: AiZheng
authors.initials: A
authors.lastname: Chen
authors.forename: TingTing
authors.initials: T
authors.lastname: Dang
authors.forename: ShiBin
authors.initials: S
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.forename: YuanGang
authors.initials: Y
authors.lastname: Liu
authors.forename: WenGuo
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D015153:Blotting, Western; D002245:Carbon Dioxide / Q000737:chemistry*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D004339:Drug Compounding; D005290:Ferric Compounds / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008727:Methotrexate / Q000737:chemistry; D051379:Mice; D008863:Microspheres; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D011091:Polyesters; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C507889:polylactide-polyethylene glycol-polylactide; D002245:Carbon Dioxide; C000499:ferric oxide; D011092:Polyethylene Glycols; D053148:Caspase 3; D008727:Methotrexate