Gelatin\u2013chlorin e6 conjugate for in vivo photodynamic therapy

Jihwan Son,Seung Mok Yang,Jae Myung Park,Bo-In Lee,Gawon Yi,Moon-Hwa Kwak,Heebeom Koo,Myung-Gyu Choi

doi:10.1186/s12951-019-0475-1

Jihwan Son, Seung Mok Yang + Show 6 more

Open Access

https://doi.org/10.1186/s12951-019-0475-1

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Abstract

BackgroundImproving the water solubility of hydrophobic photosensitizer and increasing its accumulation in tumor tissue are essential for in vivo photodynamic therapy (PDT). Considering commercialization or clinical application in future, it will be promising to achieve these purposes by developing new agents with simple and non-toxic structure.ResultsWe conjugated multiple chlorin e6 (Ce6) molecules to gelatin polymer, synthesizing two types of gelatin–Ce6 conjugates with different amounts of Ce6: gelatin–Ce6-2 and gelatin–Ce6-8. The resulting conjugates remained soluble in aqueous solutions for a longer time than hydrophobic Ce6. The conjugates could generate singlet oxygen and kill tumor cells upon laser irradiation. After intravenous injection into SCC-7 tumor-bearing mice, gelatin–Ce6-2 showed prolonged blood circulation and highly increased accumulation in tumor tissue as observed in real-time imaging in vivo. After laser irradiation, gelatin–Ce6-2 suppressed tumor growth completely and enabled improved PDT compared to free Ce6 and gelatin–Ce6-8.ConclusionsThis work demonstrates that a simple structure based on photosensitizer and gelatin can highly improve water solubility and stability. Superior tumor tissue accumulation and increased therapeutic efficacy of gelatin–Ce6 during in vivo PDT showed its high potential for clinical application.

Highlights

Improving the water solubility of hydrophobic photosensitizer and increasing its accumulation in tumor tissue are essential for in vivo photodynamic therapy (PDT)
Synthesis and characterization of gelatin–chlorin e6 conjugate Ce6 was conjugated to a gelatin polymer backbone by an amide coupling reaction between the carboxylic acid groups of Ce6 and the amine groups of gelatin (Fig. 1a)
Toxic singlet oxygen generation correlates with the amount of photosensitizer; the post-irradiation tumor cell death decreased with gelatin–Ce6 compared to free Ce6

Summary

Introduction

Improving the water solubility of hydrophobic photosensitizer and increasing its accumulation in tumor tissue are essential for in vivo photodynamic therapy (PDT). Photodynamic therapy (PDT) using photosensitizer is an effective treatment for various cancers [1]. Photosensitizer is a special kind of dye that is not toxic in the absence of light. Irradiating photosensitizer with light of the appropriate wavelength generates cytotoxic singlet oxygen and can destroy cancer cells [2]. Based on this mechanism, PDT has been used to treat colorectal, intraperitoneal, head and neck, prostate, and breast cancers [3, 4]. Photosensitizer can generate singlet oxygen and fluorescence simultaneously, which makes it useful for both imaging and therapy [3, 5,6,7].

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