@article{WU2022, 
author = {Zifei WU and Shenglin LUO and Xie HUANG and Zaizhi DU and Shaolong YUAN and Jing LIU and Weidong WANG},
title = {Synthesis of a polyethylene glycol modified indocyanine small molecule and evaluation of its anti-renal cancer cell activity},
year = {2022},
journal = {Journal of Army Medical University},
volume = {44},
number = {7},
pages = {656-664},
keywords = {indocyanine, polyethylene glycol, tumor targeting, photodynamic therapy, renal carcinoma},
url = {https://www.sciopen.com/article/10.16016/j.2097-0927.202112145},
doi = {10.16016/j.2097-0927.202112145},
abstract = {ObjectiveBased 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.MethodsPEG-modified indocyanine small molecules were designed and synthesized by using 2,3,3-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.ResultsBased 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.ConclusionOur 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.}
}