Preparation of multifunctional polyvinyl alcohol microspheres by electrospinning and its properties and application
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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。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.
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Key words:
- electrospining /
- polyvinyl alcohol /
- polydopamine /
- photothermal therapy /
- tumor therapy
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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
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)
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
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
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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