Potential of Photodynamic Therapy Based on Sugar-Conjugated Photosensitizers

Journal of Clinical Medicine

Akihiro Nomoto¹  Mamoru Tanaka²  Hiromi Kataoka²  Makiko Sasaki²  Hirotada Nishie²  Tomohiro Osaki³  Yoshiharu Okamoto³  Shigenobu Yano⁴ 

[1] Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka 599-8531, Japan;Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan;KYOUSEI Science Center for Life and Nature, Nara Women’s University, Kitauoyahigashi-machi, Nara 630-8506, Japan;

关键词: photodynamic therapy (PDT);    photosensitizer;    chlorin;    tumor-associated macrophage (TAM);    Warburg effect;   

DOI  :  10.3390/jcm10040841

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown