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用于有效且低毒光动力疗法的磁性和pH双重响应性介孔二氧化硅纳米复合材料

Magnetic and pH dual-responsive mesoporous silica nanocomposites for effective and low-toxic photodynamic therapy.

作者信息

Zhan Jieqiong, Ma Zhiqiang, Wang Dan, Li Xinfang, Li Xiangui, Le Lijing, Kang Anfeng, Hu Pengwei, She Lan, Yang Feng

机构信息

Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei.

Department of Inorganic Chemistry, School of Pharmacy.

出版信息

Int J Nanomedicine. 2017 Apr 10;12:2733-2748. doi: 10.2147/IJN.S127528. eCollection 2017.

DOI:10.2147/IJN.S127528
PMID:28442903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5396969/
Abstract

Nonspecific targeting, large doses and phototoxicity severely hamper the clinical effect of photodynamic therapy (PDT). In this work, superparamagnetic FeO mesoporous silica nanoparticles grafted by pH-responsive block polymer polyethylene glycol--poly(aspartic acid) (PEG--PAsp) were fabricated to load the model photosensitizer rose bengal (RB) in the aim of enhancing the efficiency of PDT. Compared to free RB, the nanocomposites (polyethylene glycol--polyaspartate-modified rose bengal-loaded magnetic mesoporous silica [RB-MMSNs]) could greatly enhance the cellular uptake due to their effective endocytosis by mouse melanoma B16 cell and exhibited higher induced apoptosis although with little dark toxicity. RB-MMSNs had little dark toxicity and even much could be facilitated by magnetic field in vitro. RB-MMSNs demonstrated 10 times induced apoptosis efficiency than that of free RB at the same RB concentration, both by cell counting kit-8 (CCK-8) result and apoptosis detection. Furthermore, RB-MMSNs-mediated PDT in vivo on tumor-bearing mice showed steady physical targeting of RB-MMSNs to the tumor site; tumor volumes were significantly reduced in the magnetic field with green light irradiation. More importantly, the survival time of tumor-bearing mice treated with RB-MMSNs was much prolonged. Henceforth, polyethylene glycol--polyaspartate-modified magnetic mesoporous silica (MMSNs) probably have great potential in clinical cancer photodynamic treatment because of their effective and low-toxic performance as photosensitizers' vesicles.

摘要

非特异性靶向、大剂量使用以及光毒性严重阻碍了光动力疗法(PDT)的临床效果。在本研究中,制备了由pH响应性嵌段聚合物聚乙二醇-聚天冬氨酸(PEG-PAsp)接枝的超顺磁性FeO介孔二氧化硅纳米颗粒,用于负载模型光敏剂孟加拉玫瑰红(RB),以提高光动力疗法的效率。与游离RB相比,纳米复合材料(聚乙二醇-聚天冬氨酸修饰的负载孟加拉玫瑰红的磁性介孔二氧化硅[RB-MMSNs])因其能被小鼠黑色素瘤B16细胞有效内吞,可极大地增强细胞摄取,并且尽管暗毒性较小,但显示出更高的诱导凋亡能力。RB-MMSNs暗毒性小,甚至在体外磁场作用下摄取量会进一步增加。通过细胞计数试剂盒-8(CCK-8)结果和凋亡检测发现,在相同RB浓度下,RB-MMSNs诱导凋亡的效率是游离RB的10倍。此外,RB-MMSNs介导的体内光动力疗法在荷瘤小鼠身上显示出RB-MMSNs对肿瘤部位稳定的物理靶向性;在绿光照射和磁场作用下肿瘤体积显著减小。更重要的是,用RB-MMSNs治疗的荷瘤小鼠存活时间大大延长。因此,聚乙二醇-聚天冬氨酸修饰的磁性介孔二氧化硅(MMSNs)作为光敏剂载体具有高效低毒的性能,在临床癌症光动力治疗中可能具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/b79b3f1bbb37/ijn-12-2733Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/dca311babaa8/ijn-12-2733Fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/204bfd431386/ijn-12-2733Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/46421fba20de/ijn-12-2733Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/97474683d1be/ijn-12-2733Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/876e4e8a5535/ijn-12-2733Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/7ca1ebbd6be9/ijn-12-2733Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/b79b3f1bbb37/ijn-12-2733Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/dca311babaa8/ijn-12-2733Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/eca3c6f35693/ijn-12-2733Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/243229d619b4/ijn-12-2733Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/204bfd431386/ijn-12-2733Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/46421fba20de/ijn-12-2733Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/97474683d1be/ijn-12-2733Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/876e4e8a5535/ijn-12-2733Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/7ca1ebbd6be9/ijn-12-2733Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8389/5396969/b79b3f1bbb37/ijn-12-2733Fig9.jpg

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