Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy.

Wei Liu,Shouju Wang,Yong Song,Jie Zhang,Yang Li,Yingying Jin,Yuxia Tang,Xingqun Ma

doi:10.3390/molecules26237342

Abstract

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.

Highlights

Photodynamic therapy (PDT) is based on the local activation of photosensitizers (PSs) in tumors to induce chemical damage, leading to tumor cell death [1,2]
Scheme 1 shows the synthetic route of Chlorin e6 (Ce6)-biotin
A Boc-protected amino group was linked to the biotin molecule to obtain compound 2 through Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) reaction

Summary

Introduction

Photodynamic therapy (PDT) is based on the local activation of photosensitizers (PSs) in tumors to induce chemical damage, leading to tumor cell death [1,2]. This method has become a clinically promising approach for treatment of cancers and a wide range of other diseases. The PSs activate oxygen to the singlet state and damage the nearby cells [3,4,5]. The poor selectivity of PSs to tumors is still an obstacle that severely limits their clinical application in PDT [8,9]. Much research has been devoted to improving the targeting ability of PSs

Methods

Results

Conclusion