The in vitro and in vivo anti-tumor effects of MTX-Fe3O4-PLLA-PEG-PLLA microspheres prepared by suspension-enhanced dispersion by supercritical CO2 |
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Authors: | AiZheng Chen TingTing Dang ShiBin Wang Na Tang YuanGang Liu WenGuo Wu |
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Institution: | 1. College of Chemical Engineering, Huaqiao University, Xiamen, 361021, China 2. Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen, 361021, China
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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. |
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Keywords: | methotrexate magnetic microsphere anti-tumor biological effectiveness |
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