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通过细乳液聚合合成负载锌酞菁的聚甲基丙烯酸甲酯纳米颗粒用于白血病细胞的光动力治疗。

Synthesis of ZnPc loaded poly(methyl methacrylate) nanoparticles via miniemulsion polymerization for photodynamic therapy in leukemic cells.

作者信息

Feuser Paulo Emilio, Gaspar Pamela Cristina, Jacques Amanda Virtuoso, Tedesco Antônio Claudio, Santos Silva Maria Claudia Dos, Ricci-Júnior Eduardo, Sayer Claudia, de Araújo Pedro Henrique Hermes

机构信息

Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, Brazil.

Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.

出版信息

Mater Sci Eng C Mater Biol Appl. 2016 Mar;60:458-466. doi: 10.1016/j.msec.2015.11.063. Epub 2015 Nov 27.

Abstract

The goal of this work was to synthesize and characterize ZnPc loaded poly(methyl methacrylate) (PMMA) nanoparticles (NPs) by miniemulsion polymerization. Biocompatibility assays were performed in murine fibroblast (L929) cells and human peripheral blood lymphocytes (HPBL). Finally, photobiological assays were performed in two leukemic cells: chronic myeloid leukemia in blast crisis (K562) and acute lymphoblastic leukemia (Jurkat). ZnPc loaded PMMA NPs presented an average diameter of 97±2.5 nm with a low polydispersity index and negative surface charge. The encapsulation efficiency (EE %) of ZnPc PMMA NPs was 87%±2.12. The release of ZnPc from PMMA NPs was slow and sustained without the presence of burst effect, indicating homogeneous drug distribution in the polymeric matrix. NP biocompatibility was observed on the treatment of peripheral blood lymphocytes and L929 fibroblast cells. Phototoxicity assays showed that the ZnPc loaded in PMMA NPs was more phototoxic than ZnPc after activation with visible light at 675 nm, using a low light dose of 2J/cm(2) in both leukemic cells (Jurkat and K562). The results from fluorescence microscopy (EB/OA) and DNA fragmentation suggest that the ZnPc loaded PMMA NPs induced cell death by apoptosis. Based on presented results, our study suggests that PDT combined with the use of polymeric NPs, may be an excellent alternative for leukemia treatment.

摘要

这项工作的目标是通过细乳液聚合合成并表征负载酞菁锌(ZnPc)的聚甲基丙烯酸甲酯(PMMA)纳米颗粒(NPs)。在小鼠成纤维细胞(L929)和人外周血淋巴细胞(HPBL)中进行了生物相容性测定。最后,在两种白血病细胞中进行了光生物学测定:急变期慢性髓性白血病(K562)和急性淋巴细胞白血病(Jurkat)。负载ZnPc的PMMA NPs平均直径为97±2.5 nm,多分散指数低且表面带负电荷。ZnPc PMMA NPs的包封率(EE%)为87%±2.12。ZnPc从PMMA NPs中的释放缓慢且持续,不存在突释效应,表明药物在聚合物基质中分布均匀。在对外周血淋巴细胞和L929成纤维细胞的处理中观察到了NP的生物相容性。光毒性测定表明,在675 nm可见光激活后,负载于PMMA NPs中的ZnPc在两种白血病细胞(Jurkat和K562)中,以2J/cm²的低光剂量比ZnPc具有更高的光毒性。荧光显微镜(EB/OA)和DNA片段化结果表明,负载ZnPc的PMMA NPs通过凋亡诱导细胞死亡。基于所呈现的结果,我们的研究表明,光动力疗法结合聚合物NPs的使用,可能是白血病治疗的一种极佳替代方法。

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