Synthesis of a polyethylene glycol modified indocyanine small molecule and evaluation of its anti-renal cancer cell activity

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, 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.

Keywords

• indocyanine
• polyethylene glycol
• tumor targeting
• photodynamic therapy
• renal carcinoma