聚乙二醇化吲哚花菁小分子的合成及其抗肾癌细胞活性评价

吴自飞; 罗圣霖; 黄燮; 杜在芝; 袁少隆; 刘晶; 王卫东

doi:10.16016/j.2097-0927.202112145

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聚乙二醇化吲哚花菁小分子的合成及其抗肾癌细胞活性评价

生物医学工程 | 更新时间：2026-01-09

- 聚乙二醇化吲哚花菁小分子的合成及其抗肾癌细胞活性评价
- Synthesis of a polyethylene glycol modified indocyanine small molecule and evaluation of its anti-renal cancer cell activity
- 陆军军医大学学报 2022年44卷第7期页码：656-664
- 作者机构：
  
  1.611731 成都，电子科技大学医学院附属肿瘤医院放疗中心
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系复合伤研究所，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
  
  [王卫东, E-mail: wwdwyl@sina.comWANG Weidong, E-mail: wwdwyl@sina.com
- 基金信息：
  
  国家自然科学基金面上项目(82173457);成都市科技局技术创新研发项目(2021-YF05-01659-SN)
- DOI：10.16016/j.2097-0927.202112145
  中图分类号： R914.2;R965;R979.1
- 收稿：2021-12-17，
  
  修回：2022-01-26，
  
  纸质出版：2022-04-15
- 稿件说明：
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吴自飞, 罗圣霖, 黄燮, 等. 聚乙二醇化吲哚花菁小分子的合成及其抗肾癌细胞活性评价[J]. 陆军军医大学学报, 2022,44(7):656-664.

Zifei WU, Shenglin LUO, Xie HUANG, et al. Synthesis of a polyethylene glycol modified indocyanine small molecule and evaluation of its anti-renal cancer cell activity[J]. Journal of Army Medical University, 2022, 44(7): 656-664.
吴自飞, 罗圣霖, 黄燮, 等. 聚乙二醇化吲哚花菁小分子的合成及其抗肾癌细胞活性评价[J]. 陆军军医大学学报, 2022,44(7):656-664. DOI： 10.16016/j.2097-0927.202112145.

Zifei WU, Shenglin LUO, Xie HUANG, et al. Synthesis of a polyethylene glycol modified indocyanine small molecule and evaluation of its anti-renal cancer cell activity[J]. Journal of Army Medical University, 2022, 44(7): 656-664. DOI： 10.16016/j.2097-0927.202112145.

摘要

目的

在前期发现具有肿瘤靶向性的吲哚花菁小分子的结构基础上，对其进行聚乙二醇(polyethylene glycol

PEG)水溶性修饰，并评价其理化性质和肿瘤靶向光动力治疗作用。

方法

分别以2

3-三甲基吲哚、聚乙二醇单甲醚为原料，设计并化学合成PEG修饰吲哚花菁小分子，采用核磁氢谱、质谱等检测、表征其化学结构；通过水溶性比较、光学性质表征、肾脏正常细胞HK-2与肿瘤细胞RENCA摄入比较、细胞活力测试、单线态氧以及细胞活性氧测定等，评价其理化性质与肿瘤靶向光动力作用。

结果

通过汇聚合成策略，经过6步化学反应，成功合成PEG修饰的吲哚花菁小分子PEG-808-NM2，其结构经核磁氢谱、质谱等确证。与808-NM2相比，PEG-808-NM2水溶性显著增加，在甲醇和PBS中均表现出优异的近红外荧光特性。PEG-808-NM2优先被肾癌细胞RENCA摄取，并在808 nm激光照射下，诱导产生大量的单线态氧和细胞内活性氧自由基。

结论

合成的PEG-808-NM2在保留吲哚花菁小分子原有的肿瘤靶向、近红外成像作用基础上显著改善其理化及光敏特性，对肾癌细胞具有显著的光动力治疗作用。

Abstract

Objective

Based on previous studies on a class of tumor-targeted indocyanine small molecules

we aimed to synthesize a new analog modified with water-soluble polyethylene glycol (PEG) and then investigated its physicochemical properties and role in tumor targeting photodynamic therapy.

Methods

PEG-modified indocyanine small molecules were designed and synthesized by using 2

3-trimethylindole and polyethylene glycol monomethyl ether as raw materials. Its chemical structure was characterized by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS); its physicochemical properties and cancer targeting photodynamic effect were investigated by determining its water solubility

optical spectra

cell uptake

cell viability

singlet oxygen

and reactive oxygen production.

Results

Based on a converging strategy of synthesis and through 6 steps of chemical reactions

a PEG-modified indocyanine small molecule (PEG-808-NM2) was successfully produced. Its structure was confirmed by NMR spectroscopy and MS. Compared to 808-NM2

PEG-808-NM2 significantly increased water solubility and exhibited excellent near-infrared fluorescence property in both methanol and water solution. PEG-808-NM2 preferentially accumulated in RENCA cells (a mouse renal adenocarcinoma cell line) rather than HK-2 cells (a tubular cell line from normal human kidneys). Under 808 nm-laser irradiation

PEG-808-NM2 induced a great amount of singlet oxygen and intracellular reactive oxygen species.

Conclusion

Our synthesized PEG-modified indocyanine small molecules not only keep the cancer preferential accumulation and the role in near-infrared imaging as original indocyanine

but also obtain significantly improved physicochemical properties and photosensitizing effect. They exert significant photodynamic therapeutic effect on renal cell carcinoma cells.

关键词

Keywords

references

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