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基于二硒键连接的氯代脱镁叶绿酸 e6 偶联 β-环糊精纳米光敏剂用于宫颈癌细胞的氧化还原和叶酸受体双重靶向光动力学治疗。

Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage.

机构信息

Department of Medicine, Graduate School, Dongguk University, Gyeongju 38067, Korea.

Department of Anesthesiology and Pain Medicine, College of Medicine, Dongguk University, Gyeongju 38067, Korea.

出版信息

Cells. 2021 Aug 25;10(9):2190. doi: 10.3390/cells10092190.

DOI:10.3390/cells10092190
PMID:34571839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8465130/
Abstract

The aim of this study was to fabricate a reactive oxygen species (ROS)-sensitive and folate-receptor-targeted nanophotosensitizer for the efficient photodynamic therapy (PDT) of cervical carcinoma cells. Chlorin e6 (Ce6) as a model photosensitizer was conjugated with succinyl β-cyclodextrin via selenocystamine linkages. Folic acid (FA)-poly(ethylene glycol) (PEG) (FA-PEG) conjugates were attached to these conjugates and then FA-PEG-succinyl β-cyclodextrin-selenocystamine-Ce6 (FAPEGbCDseseCe6) conjugates were synthesized. Nanophotosensitizers of FaPEGbCDseseCe6 conjugates were fabricated using dialysis membrane. Nanophotosensitizers showed spherical shapes with small particle sizes. They were disintegrated in the presence of hydrogen peroxide (HO) and particle size distribution changed from monomodal distribution pattern to multimodal pattern. The fluorescence intensity and Ce6 release rate also increased due to the increase in HO concentration, indicating that the nanophotosensitizers displayed ROS sensitivity. The Ce6 uptake ratio, ROS generation and cell cytotoxicity of the nanophotosensitizers were significantly higher than those of the Ce6 itself against HeLa cells in vitro. Furthermore, the nanophotosensitizers showed folate-receptor-specific delivery capacity and phototoxicity. The intracellular delivery of nanophotosensitizers was inhibited by folate receptor blocking, indicating that they have folate-receptor specificity in vitro and in vivo. Nanophotosensitizers showed higher efficiency in inhibition of tumor growth of HeLa cells in vivo compared to Ce6 alone. These results show that nanophotosensitizers of FaPEGbCDseseCe6 conjugates are promising candidates as PDT of cervical cancer.

摘要

本研究旨在制备一种活性氧(ROS)敏感和叶酸受体靶向的纳米光敏剂,用于高效光动力治疗(PDT)宫颈癌细胞。氯乙酮(Ce6)作为模型光敏剂通过硒代半胱氨酸键与琥珀酰-β-环糊精偶联。将叶酸(FA)-聚乙二醇(PEG)(FA-PEG)缀合物连接到这些缀合物上,然后合成 FA-PEG-琥珀酰-β-环糊精-硒代半胱氨酸-Ce6(FAPEGbCDseseCe6)缀合物。使用透析膜制备 FAPEGbCDseseCe6 缀合物的纳米光敏剂。纳米光敏剂呈球形,粒径较小。它们在过氧化氢(HO)的存在下崩解,粒径分布从单模态分布模式变为多模态模式。荧光强度和 Ce6 释放率也随着 HO 浓度的增加而增加,表明纳米光敏剂具有 ROS 敏感性。与 Ce6 本身相比,纳米光敏剂在体外对 HeLa 细胞的 Ce6 摄取率、ROS 生成和细胞细胞毒性均显著升高。此外,纳米光敏剂表现出叶酸受体特异性递药能力和光毒性。通过叶酸受体阻断抑制了纳米光敏剂的细胞内递送,表明它们在体外和体内均具有叶酸受体特异性。与单独使用 Ce6 相比,纳米光敏剂在体内抑制 HeLa 细胞生长的效率更高。这些结果表明,FAPEGbCDseseCe6 缀合物的纳米光敏剂是宫颈癌 PDT 的有前途的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/e70a72f7e0f6/cells-10-02190-g012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/e70a72f7e0f6/cells-10-02190-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/82dae3b95535/cells-10-02190-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/ca94530f04d0/cells-10-02190-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/16eb370fe848/cells-10-02190-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/0ae2aae25ed5/cells-10-02190-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/ae0fd06f30cb/cells-10-02190-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/f03ce4fd2100/cells-10-02190-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/8465130/e70a72f7e0f6/cells-10-02190-g012.jpg

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