纺锤状羟基氧化铁@聚吡咯复合纳米粒子的制备及其光热治疗肿瘤应用

黄漂; 易昌凤; 徐祖顺

doi:10.13801/j.cnki.fhclxb.20211014.002

纺锤状羟基氧化铁@聚吡咯复合纳米粒子的制备及其光热治疗肿瘤应用

doi: 10.13801/j.cnki.fhclxb.20211014.002

湖北大学　材料科学与工程学院，武汉 430062

基金项目: 国家自然科学基金 (51573039)

详细信息

通讯作者:
易昌凤，硕士，教授，硕士生导师，研究方向为乳液聚合、超支化聚合物、特种涂料等　E-mail：changfengyi@hubu.edu.cn

中图分类号: TB302
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出版历程
- 收稿日期: 2021-07-06
- 修回日期: 2021-08-19
- 录用日期: 2021-08-27
- 网络出版日期: 2021-10-15
- 刊出日期: 2022-07-30

Preparation of spindle-shaped hydroxyl ferric oxide@polypyrrole composite nanoparticles and its application in photothermal therapy of tumors

School of Materials Science and Engineering, Hubu University, Wuhan 430062, China

摘要

摘要: 肿瘤是世界上死亡率最高的疾病，研制新型肿瘤药物也是一项极具开发性的研究。首先制备纺锤状羟基氧化铁纳米粒子(FeOOH NPs)并作为模板，与吡咯(Py)聚合得到纺锤状羟基氧化铁@聚吡咯(FeOOH@PPy)复合纳米粒子。采用FTIR、DLS、TEM和UV-vis等测试方法对FeOOH@PPy进行了结构、性质表征，通过光热转换实验证明了该复合纳米粒子具有优异的光热转换性能，探究了复合纳米粒子的生物相容性以及肿瘤治疗中的应用潜力。结果表明，所得到的复合纳米粒子平均粒径100 nm左右，且分布均一，粒子呈纺锤状结构，在水溶液中具有良好的稳定性。FeOOH@PPy复合纳米粒子可以吸收808 nm的近红外光，并将其转化为足够的热量，使肿瘤细胞凋亡；在为期14天的4T1细胞的小鼠模型体内治疗实验中，FeOOH@PPy复合纳米粒子治疗组表现出优异的治疗肿瘤效果，组织分析表明FeOOH@PPy复合纳米粒子对小鼠正常组织无明显影响，具有作为光热治疗剂的潜力。
- 纳米材料 /
- 聚吡咯 /
- 光热性能 /
- 生物相容性 /
- 肿瘤治疗
Abstract: Cancer is a disease with the highest mortality rate in the world, developing new cancer drugs is also a very exploratory research. In this paper, spindle-shaped iron hydroxyl oxide (FeOOH NPs) was firstly prepared as a nanocarrier to polymerise pyrrole (Py) to get iron hydroxyl oxide @polypyrrole (FeOOH@PPy) composite nano-material. The structure and properties of FeOOH@PPy were characterized by FTIR, DLS, TEM and UV-vis, etc. The photothermal conversion experiments proved that the composite nanoparticles had excellent photothermal conversion properties, and the biocompatibility and application potential of the composite nanomaterial in tumor therapy were explored. The results show that the average particle size of the obtained nanoparticles is about 100 nm, and has good stability in the aqueous solution. The results of the photothermal performance test show that FeOOH@PPy composite nanoparticles can absorb 808 nm near-infrared light and convert it into enough heattotrigger the apoptosis of tumor cells. In a 14 days treatment on 4T1 breast cancer mouse model, FeOOH@PPy composite nanoparticles show excellent antitumor effect. Tissue analysis show that the composite nanoparticles have no significant effect on normal tissues of mice, suggesting that the composite nanoparticles have the potential as photothermal therapy agent.
- nanomaterials /
- polypyrrole /
- photothermal performance /
- biocompatibility /
- tumor therapy

HTML全文

图 1 羟基氧化铁@聚吡咯(FeOOH@PPy)复合纳米粒子的合成路线图

Figure 1. Synthesis route of iron hydroxyl oxide@polypyrrole (FeOOH@PPy)

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图 2 (a) FeOOH的FESEM图像；(b) FeOOH@PPy的TEM图像

Figure 2. (a) FESEM image of FeOOH; (b) TEM image of FeOOH@PPy

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图 3 动态光散射(DLS)测量的FeOOH@PPy粒径

Figure 3. Size of FeOOH@PPy measured by dynamic light scattering (DLS)

PDI—Polymer dispersity index

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图 4 FeOOH@BSA和FeOOH@PPy的FTIR图谱

Figure 4. FTIR spectra of FeOOH@BSA and FeOOH@PPy

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图 5 FeOOH@BSA和FeOOH@PPy紫外吸收图谱

Figure 5. UV-vis spectras of FeOOH@BSA and FeOOH@PPy with same concentration (40 μg/mL)

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图 6 FeOOH@PPy分散在去离子水、PBS、生理盐水和DMEM照片(a)；7天内FeOOH@PPy在PBS(b)、生理盐水(c)、DMEM (d)中的粒径对比图

Figure 6. Digital photos of FeOOH@PPy dispersions in water, PBS, saline and DMEM (a); DLS analysis of the size change of FeOOH@PPy in PBS (b), saline (c) and DMEM (d) in 7 days.

PBS—Phosphate buffered solution; DMEM—Dulbecco's modified eagle medium

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图 7 (a) FeOOH@PPy浓度为0~320 μg/mL的水溶液中的溶血测定图；(b)不同浓度下FeOOH@PPy的相对溶血率

Figure 7. (a) Hemolysis assay of FeOOH@PPy in aqueous solutions with FeOOH@PPy concentrations of 0-320 μg/mL; (b) Relative hemolysis percentages based on concentrations with FeOOH@PPy

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图 8 (a)不同浓度下的FeOOH@PPy的紫外-可见吸收图谱；(b)不同浓度FeOOH@PPy在808 nm处的吸光度的线性拟合曲线，附图为相关FeOOH@PPy分散体的照片；(c)不同浓度FeOOH@PPy在近红外激光(808 nm，1.5 W/cm²)照射10 min的温度变化曲线；(d)不同浓度对应样品的热成像

Figure 8. (a) UV-vis absorbance spectrum of FeOOH@PPy under different concentrations in water; (b) Liner fitting of the concentration of FeOOH@PPy to their absorbance at 808 nm, and the inset shows the digital photos of relevant FeOOH@PPy dispersions; (c) Temperature elevation of various concentrations of FeOOH@PPy under the NIR laser irradiation (808 nm,1.5 W/cm²) for 10 min; (d) Thermal imaging of corresponding samples under different concentrations

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图 9 (a) FeOOH@PPy (160 μg/mL)的热循环曲线；(b) FeOOH@PPy循环前后的紫外-可见吸收光谱

Figure 9. (a) Circulation curve of FeOOH@PPy (160 μg/mL); (b) UV-vis absorbance spectra of FeOOH@PPy before and after circulation

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图 10 4T1细胞在不同浓度FeOOH@BSA和FeOOH@PPy孵育条件下的细胞活力图

Figure 10. The cells viability of 4T1 cells under different condition incubated with different concentrations of FeOOH@BSA and FeOOH@PPy

Calcein-AM—Calcein acetoxymethyl ester; PI—Propidium iodide

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图 11 空白对照组(PBS)、激光照射对照组(PBS(+))、FeOOH@PPy对照组(FeOOH@PPy)、FeOOH@PPy激光照射组(FeOOH@PPy(+))：(a)不同处理后的体重变化图；(b)不同治疗后肿瘤相对体积变化图

Figure 11. Blank control group (PBS), laser irradiation control group (PBS(+)), FeOOH@PPy control group (FeOOH@PPy), FeOOH@PPy laser irradiation group (FeOOH@PPy(+)): (a) Relative body weight after different treatment; (b) Relative tumor volume change after different treatment

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图 12 用FeOOH@PPy和PBS做相应处理后的小鼠主要器官的H&E染色图像

Figure 12. H&E stained images of major organs from FeOOH@PPy treated mice and PBS treated mice

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