Potential of Photodynamic Therapy Based on Sugar-Conjugated Photosensitizers.

Hiromi Kataoka,Tomohiro Osaki,Shigenobu Yano,Hirotada Nishie,Mamoru Tanaka,Makiko Sasaki,Yoshiharu Okamoto,Akihiro Nomoto

doi:10.3390/jcm10040841

Abstract

In 2015, the Japanese health insurance approved the use of a second-generation photodynamic therapy (PDT) using talaporfin sodium (TS); however, its cancer cell selectivity and antitumor effects of TS PDT are not comprehensive. The Warburg effect describes the elevated rate of glycolysis in cancer cells, despite the presence of sufficient oxygen. Because cancer cells absorb considerable amounts of glucose, they are visible using positron emission tomography (PET). We developed a third-generation PDT based on the Warburg effect by synthesizing novel photosensitizers (PSs) in the form of sugar-conjugated chlorins. Glucose-conjugated (tetrafluorophenyl) chlorin (G-chlorin) PDT revealed significantly stronger antitumor effects than TS PDT and induced immunogenic cell death (ICD). ICD induced by PDT enhances cancer immunity, and a combination therapy of PDT and immune checkpoint blockers is expected to synergize antitumor effects. Mannose-conjugated (tetrafluorophenyl) chlorin (M-chlorin) PDT, which targets cancer cells and tumor-associated macrophages (TAMs), also shows strong antitumor effects. Finally, we synthesized a glucose-conjugated chlorin e6 (SC-N003HP) that showed 10,000–50,000 times stronger antitumor effects than TS (IC50) in vitro, and it was rapidly metabolized and excreted. In this review, we discuss the potential and the future of next-generation cancer cell-selective PDT and describe three types of sugar-conjugated PSs expected to be clinically developed in the future.

Highlights

Photodynamic therapy (PDT) is a mildly invasive anticancer therapy that combines a photosensitizer (PS) and a specific wavelength of light irradiation to generate reactive oxygen species (ROS) to destroy cancer cells
Glucose transporter 1 (GLUT1) overexpression has been observed in a broad spectrum of cancers, and GLUT, especially GLUT1, expression is correlated to unfavorable outcomes in patients with cancer [23]
From the different members of the tumor microenvironment, we focused on the specific immune cells of tissue macrophages, which are key regulators of the relationship between the immune system and the tumor

Summary

Introduction

Photodynamic therapy (PDT) is a mildly invasive anticancer therapy that combines a photosensitizer (PS) and a specific wavelength of light irradiation to generate reactive oxygen species (ROS) to destroy cancer cells. GLUT1 overexpression has been observed in a broad spectrum of cancers, and GLUT, especially GLUT1, expression is correlated to unfavorable outcomes in patients with cancer [23] Considering these points, we utilized our understanding of the Warburg effect to develop a third-generation PS as part of a novel PDT, which possesses cancer cell specificity and selectivity. GLUT1 overexpression has been observed in a broad spectrum o cancers, and GLUT, especially GLUT1, expression is correlated to unfavorable outcome in patients with cancer [23] We used the GIST cell line and GIST-T1 cells to confirm that G-chlorin PDT shows strong antitumor effects against GIST in a xenograft model [30]

PDT Enhances Tumor Immunity

Other Expected Photosensitizers

Phthalocyanine

Indocyanine Green