Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

Sven Kruspe,Ulrich Hahn,Cindy Meyer

doi:10.1038/mtna.2013.70

Abstract

Photodynamic therapy (PDT) uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6) with a human interleukin-6 receptor (IL-6R) binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+) cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

Highlights

Photodynamic therapeutic agents Photodynamic therapy (PDT) is clinically used as a nonsurgical treatment option for several diseases, such as malignant cancers
We recently described the interleukin-6 receptor (IL-6R)–specific RNA aptamer (AIR-3A), which is internalized by cells through receptor-mediated endocytosis (RME).[15]
Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Kruspe et al Results Construction of the chlorin e6 aptamer conjugate AIR-3A-ce[6] To conjugate the RNA aptamer AIR-3A and the photosensitizer ce[6], we directly linked an aminomodified version of AIR3A to ce[6] through an EDC-/NHS-mediated amine coupling as outlined in the Materials and Methods

Summary

Introduction

Photodynamic therapeutic agents Photodynamic therapy (PDT) is clinically used as a nonsurgical treatment option for several diseases, such as malignant cancers. PDT uses photosensitizing agents, called photosensitizers, that accumulate more or less selectively in target cells.[1,2]. Photosensitizers, such as chlorins (e.g., Tomoporphin sold as Foscan),[3,4] are excited from the singlet electron ground state to a higher singlet state upon illumination with light sources of the appropriate wavelength, typically 600–800 nm. We recently described the interleukin-6 receptor (IL-6R)–specific RNA aptamer (AIR-3A), which is internalized by cells through RME.[15]. A promising therapeutic strategy to tackle the aforementioned diseases might be to deliver drugs into cells by selectively targeting IL-6R. We report AIR-3A as a specific and efficient delivery system for the PDT agent chlorin e6 into IL-6R presenting cells and the subsequent induction of cell death upon irradiation. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Kruspe et al

Results

Discussion

Materials and methods