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Preparation of IL-2-loaded magnetic nanoparticle and its targeting accumulation in tumor tissues combining with external magnetic field
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Abstract:
Objective:To prepare IL-2-loaded magnetic nanoparticle (IL-2-Fe3O4-PLGA) with Fe3O4 magnetic nano-particle (Fe3O4-MNP) and poly lactide-co-glycolide (PLGA), and to investigate its targeted accumulation function in tumor immunotherapy. Methods: The double emulsion method was employed for preparation of IL-2-Fe3O4-PLGA, its size and morphology were observed with a laser particle size analyzer and under a scanning electron microscope, respectively. In addition, the drug encapsulation efficiency and releasing characteristics of IL-2-Fe3O4-PLGA in vitro were measured with ELISA. The biological activity of the IL-2 released from the IL-2-Fe3O4-PLGA was evaluated by MTT assay. Sarcoma 180 cell-transplanted tumor mouse model was established to study the effect of IL-2-Fe3O4-PLGA in combination with external magnetic field on the growth of Sarcoma 180 tumors. The tumor, liver and kidney tissues were examined by Prussian blue staining to determine the accumulation and distribution of the IL-2-Fe3O4-PLGA in the tissue sections. Results: IL-2-Fe3O4-PLGA was constructed successfully, and was spherical with a mean diameter of (697±0.51) nm as well as a drug encapsulation efficiency of (83.76±1.24) %. In the drug release test in vitro, the mass concentration of released IL-2 was 100 ng/ml during the burst release phase and rose to 180 ng/ml at the end of 15 d. Moreover, the released IL-2 remained 85%-55% of its original activity during the releasing period. A strong IL-2-Fe3O4-PLGA positive reaction was observed in IL-2-Fe3O4-PLGA-treated mice combined with an external magnetic field, but only a weak reaction in mice injected with IL-2-Fe3O4-PLGA alone. Furthermore, in both groups, Prussian blue-stained liver showed occasionally light IL-2-Fe3O4-PLGA positive staining, while IL-2-Fe3O4-PLGA positive reaction was rarely detected in the kidneys. Conclusion: IL-2 loaded magnetic nanoparticle IL-2-Fe3O4-PLGA has controlled IL-2-release function and targeting accumulation capability in tumor tissues when combined with an external magnetic field.
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Project Supported:
Project supported by the National High Technology Research and Development Program (863 Program) (No. 2007AA021806)
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