静电纺丝法制备多功能聚乙烯醇微球及其性能和应用

王世革; 徐霞; 陈永康; 叶长青; 安潇

doi:10.13801/j.cnki.fhclxb.20200928.002

静电纺丝法制备多功能聚乙烯醇微球及其性能和应用

doi: 10.13801/j.cnki.fhclxb.20200928.002

王世革^1,,
徐霞^1,,
陈永康^1,,
叶长青^1,,
安潇^{1, 2, ,}

1.
上海理工大学　理学院，上海 200093
2.
上海市第一人民医院　肿瘤介入科，上海 200080

基金项目: 上海市青年科技启明星计划(20QA1407200)；上海市浦江人才计划(18PJD040)；国家自然科学基金(81972904；51702214)

详细信息

通讯作者:
安潇，博士，副主任医师，研究方向为肿瘤的介入治疗和纳米材料的应用　E-mail: 54andromeda@163.com

中图分类号: TB332
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- 被引次数: 0
出版历程
- 收稿日期: 2020-07-16
- 录用日期: 2020-09-27
- 网络出版日期: 2020-09-28
- 刊出日期: 2021-06-23

Preparation of multifunctional polyvinyl alcohol microspheres by electrospinning and its properties and application

WANG Shige^1
,,
XU Xia^1
,,
CHEN Yongkang^1
,,
YE Changqing^1
,,
AN Xiao^{1, 2
, ,}

1.
College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China
2.
Oncology Interventional Department, Shanghai First People’s Hospital, Shanghai 200080, China

摘要

摘要: 通过静电纺丝法，制备了MnO₂-聚多巴胺(PDA)/聚乙烯醇(PVA)和MnO₂-PDA-5-氟尿嘧啶(5-Fu)/PVA复合微球。具体地，在PVA溶液中依次加入多巴胺(DA)与KMnO₄，在所得溶液中，DA与KMnO₄发生氧化还原反应，原位聚合生成PDA，而KMnO₄转变为MnO₂，通过静电纺丝法制备了MnO₂-PDA/PVA微球。向上述溶液中加入化疗药物5-Fu，通过静电纺丝法还可以制备MnO₂-PDA-5-Fu/PVA微球。通过戊二醛交联赋予静电纺丝微球水稳定性。这一复合微球材料具有优异的光热转换性能、可控的药物缓释性能及良好的生物安全性，被应用于防止术后肿瘤的复发。一方面，在808 nm NIR激光照射下MnO₂-PDA-5-Fu/PVA微球的光热转换效率可达到24.5%，实现高效的肿瘤热消融；另一方面，释放出来的5-Fu可杀死术后残余的肿瘤细胞。该研究论证了静电纺丝法制备复合微球的可行性，并证实了这种微球在防止肿瘤术后复发领域的应用潜力，为多功能复合微/纳米材料的设计提供了新策略。
- 静电纺丝 /
- 聚乙烯醇 /
- 聚多巴胺 /
- 光热治疗 /
- 肿瘤治疗
Abstract: In this paper, MnO₂-polydopamine (PDA)/polyvinyl alcohol (PVA) and MnO₂-PVA-5-fluorouracil (5-Fu)/PVA composite microspheres were prepared by electrospinning. Specifically, dopamine (DA) and KMnO₄ were added to the PVA solution, where a redox reaction happened between DA and KMnO₄ to form PDA and MnO₂. Thus, the MnO₂-PDA/PVA microspheres were prepared by electrospinning the MnO₂-PDA/PVA solution. MnO₂-PDA-5-Fu/PVA microspheres were prepared by electrospinning the MnO₂-PDA-5-Fu/PVA solution, which was prepared by directly dissolving 5-Fu in the MnO₂-PDA/PVA solution. The water stability of the electrospun microspheres was given by a glutaraldehyde crosslinking method. The composite microspheres have excellent photothermal conversion, controlled drug release and good biosafety, which were used to prevent the recurrence of tumor after the operation. The photothermal conversion efficiency of MnO₂-PDA-5-Fu/PVA microspheres reaches 24.5% under the irradiation of 808 nm NIR laser, which can achieve the efficient tumor thermal ablation; on the other hand, the released 5-Fu can kill the residual tumor cells after operation. This study confirms the application potential of the microspheres in the field of preventing tumor recurrence, and provides a new strategy for the design of multifunctional composite nanomaterials.
- electrospining /
- polyvinyl alcohol /
- polydopamine /
- photothermal therapy /
- tumor therapy

HTML全文

图 1 静电纺丝制备MnO₂-聚多巴胺(PDA)/聚乙烯醇(PVA) 的示意图 (a)、未交联的MnO₂-PDA/PVA (b) 和MnO₂-PDA-5-氟尿嘧啶(5-Fu)/PVA (c) 的SEM图像、交联后的MnO₂-PDA/PVA (d) 和MnO₂-PDA-5-Fu/PVA (e) 的SEM图像

Figure 1. Schematic diagram of electrospinning MnO₂-polydopamine (PDA)/polyvinyl alcohol (PVA) (a), SEM images of uncrosslinked MnO₂-PD/PVA (b) and MnO₂-PDA-5-fluorouracil (5-Fu)/PVA (c), SEM images of MnO₂-PDA/PVA (d) and MnO₂-PDA-5-Fu/PVA (e) after crosslinking

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图 2 MnO₂-PDA/PVA复合微球的粒径分布 (a)、MnO₂-PDA/PVA的FTIR图谱 (b)、MnO₂-PDA/PVA的XPS图谱 (c)、MnO₂-PDA/PVA的热重曲线 (d)

Figure 2. Particle size distribution of the microspheres (a), FTIR spectra of different samples(b), XPS spectra of MnO₂-PDA/PVA (c) , thermogravimetric curves of MnO₂-PDA/PVA (d)

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图 3 不同溶液的光吸收谱图 (a)、不同激光密度下微球的光热性能曲线 (b)、对应于图3(b)的光热成像照片 (c)、光热转换效率曲线 (d)、光热稳定性曲线 (e)

Figure 3. Light absorption of different solutions (a), photothermal performance curves under different laser densities (b), photothermal imaging photographs corresponding to fig. 3(b) (c), photothermal conversion efficiency curve (d), photothermal stability curve of MnO₂-PVA/PDA (e)

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图 4 材料溶血性能测试结果 (a)、与材料共培养的HT29和L929细胞的存活率 (b)、对应于图4(b)的细胞形貌图 (c)

Figure 4. Hemolysis test results of materials (a), survival rate of HT29 and L929 cells co-cultured with the material (b), morphologic picture of the corresponding fig. 4(b) (c)

P_H—Hemolysis ratio

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图 5 不同条件下5-Fu药物的释放动力学 (a)、细胞水平肿瘤治疗效果 (b)、对应于图5(b)的死/活细胞染色图片 ((c)~(f))

Figure 5. Release kinetics of 5-Fu under different conditions (a), tumor therapeutic effects in vitro (b), dead/live staining pictures corresponding to fig. 5(b) ((c)-(f))

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图 6 对照组小鼠和实验组小鼠在14天内的体重变化 (a)、血清生化因子 (b)、不同时间点小鼠主要器官中Mn元素的分布含量 (c)、小鼠主要器官的H&E染色 (d)

Figure 6. Body weight changes of control and experimental mice within 14 days (a), serum biochemical factors (b), distribution and content of Mn in main organs of mice at different time points (c), H&E staining of main organs of mice (d)

TB—Total bilirubin; ALT—Alanine transaminase; AST—Aspartate aminotransferase

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图 7 不同时间点的KM鼠血常规参数

Figure 7. Blood routine parameters of KM mice at different time points

WBC—White blood cell count; RBC—Red blood cell count; HB—Hemoglobin; HCT—Hematocrit; MCV—Corpuscular volume; MCH—Corpuscular hemoglobin; MCHC—Corpuscular hemoglobin concentration; RDW—Red cell distribution width; PLT—Platelet

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图 8 小鼠光热治疗的温度变化曲线 (a)；对应图8(a)小鼠的热成像照片 (b)；不同实验组小鼠的肿瘤体积变化曲线 (c)；治疗前肿瘤照片 (d)；治疗后第28天：对照组 (e)、MnO₂-PVA/PDA+NIR (f)、MnO₂-PDA-5-FU/PVA (g)和MnO₂-PDA-5-FU/PVA+NIR (h) 治疗过程小鼠肿瘤的图片

Figure 8. Temperature curve of mice after the photothermal therapy (a); tumor photothermal imaging corresponding to fig.8(a) (b); tumor volume change curves of mice in different experimental groups (c); tumor photograph before therapy (d); mouse photographs at day 28 after the therapy: Control group (e), MnO₂-PVA/PDA+NIR (f), MnO₂-PDA-5-FU/PVA (g) and MnO₂-PDA-5-FU/PVA+NIR (h)

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