A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

Hayashi, Noriyuki; Kataoka, Hiromi; Yano, Shigenobu; Tanaka, Mamoru; Moriwaki, Kazuhiro; Akashi, Haruo; Suzuki, Shugo; Mori, Yoshinori; Kubota, Eiji; Tanida, Satoshi; Takahashi, Satoru; Joh, Takashi

doi:10.1158/1535-7163.mct-14-0348

Cited by 67 publications

(55 citation statements)

References 46 publications

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“…Therefore, G-chlorin is a potential photosensitizer of PDT for treating gastric and colon cancer and GIST in vitro and in vivo [19, 20]. Furthermore, we found that PDT with mannose-conjugated chlorin displayed very strong anticancer effects [21]. …”

Section: Introductionmentioning

confidence: 99%

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

et al. 2016

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Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release.

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Section: Introductionmentioning

confidence: 99%

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

et al. 2016

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“…In an in vivo allograft model study, M-chlorin PDT showed the strongest antitumor effects. The number of TAMs in the cancer tissue after PDT was significantly decreased in the M-chlorin group compared to the other groups (chlorin and G-chlorin) (19).…”

Section: Targeting Tumor-associated Macrophages (Tams) In Cancer Tissmentioning

confidence: 72%

New photodynamic therapy with next-generation photosensitizers

Kataoka¹,

Nishie²,

Hayashi³

et al. 2017

Ann. Transl. Med.

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118

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Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate.Cancer cells consume higher levels of glucose than normal cells and this phenomenon is known as the Warburg effect. Thus, we developed a third-generation PDT, based on the Warburg effect, by synthesizing a novel photosensitizer, sugar-conjugated chlorin, with increased cancer cell-selective accumulation. Glucose-conjugated chlorin (G-chlorin) PDT showed significantly stronger antitumor effects than second-generation talaporfin PDT.We also found that PDT with G-chlorin induced immunogenic cell death which is characterized by the secretion, release, or surface exposure of damage-associated molecular patterns (DAMPs), including calreticulin (CRT) and the high-mobility group box 1 (HMGB1) protein. Mannose-conjugated chlorin (M-chlorin) PDT which targets the mannose receptors on the surface of cancer cells and tumor-associated macrophages (TAMs) in cancer tissue stroma also showed very strong antitumor effects. These novel PDTs using glucose or M-chlorins stand as new candidates for very effective, next-generation PDTs.

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“…We observed the remarkable PDT effect with H 2 TFPC-SMan for in vitro and in vivo investigations in the previous report. 32 Thus, H 2 TFPCSMan has great potential for use as a PDT and a photodynamic diagnostic agent. …”

Section: Resultsmentioning

confidence: 99%

“…TAMs are known to specifically express abundant levels of CD206, a mannose receptor, 2931 which is also called the pattern-recognition receptor. We recently reported a remarkable PDT effect with a newly prepared mannose-conjugated chlorin (H 2 TFPCSMan = 5,10,15,20-tetrakis(4-(α-D-mannopyranosylthio)-2,3,5,6-tetrafluorophenyl)-2,3-(methano-(N-methyl)iminomethano)chlorin) designed to bind mannose receptors highly expressed on TAMs and evaluated PDT with H 2 TFPC-SMan for in vitro cytotoxicity and apoptosis induction in gastric and colon cancer cells 32 as compared with chlorin (H 2 TFPC = 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(methano(N-methyl)iminomethano)chlorin) alone and glucose-conjugated chlorin (H 2 TFPC-SGlc = 5,10,15,20-tetrakis(4-(β-D-glucopyranosylthio)-2,3,5,6-tetrafluorophenyl)-2,3-(methano(Nmethyl)iminomethano)chlorin). 17,18,2831 Here, we wish to report the detailed synthetic procedure of mannose-conjugated chlorin (H 2 TFPC-SMan) and its PDT effect in HeLa cells, including an X-ray crystal structure of 2,3,4,6-tetra-O-acetyl-1-S-acetyl-α-D-mannopyranose (AcManSAc), since no descriptions of any synthetic procedures were described in the previous report.…”

Section: Introductionmentioning

confidence: 99%

“…17,18,2831 Here, we wish to report the detailed synthetic procedure of mannose-conjugated chlorin (H 2 TFPC-SMan) and its PDT effect in HeLa cells, including an X-ray crystal structure of 2,3,4,6-tetra-O-acetyl-1-S-acetyl-α-D-mannopyranose (AcManSAc), since no descriptions of any synthetic procedures were described in the previous report. 32 …”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Photophysical Properties of S-Mannosylated Chlorins and Their Effect on Photocytotoxicity in HeLa Cells

Moriwaki

Sawada

Akiyama

et al. 2018

Bulletin of the Chemical Society of Japan

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SMan and H 2 TFPC-SGlc were tested in HeLa cells. These compounds showed no cytotoxicity in the dark. Upon photoirradiation, these compounds killed almost all of the cells in the region of a 1 to 2¯M concentration. The photocytotoxicity of the compounds completely disappeared in the concentration region of 0 to 0.1¯M. The photocytotoxicity of H 2 TFPCSMan is significantly higher than that of H 2 TFPC-SGlc in the concentration range from 0.2 to less than 1¯M. The cellular uptake of H 2 TFPC-SMan in HeLa cells was estimated in terms of fluorescence intensity from each HeLa cell. The cellular uptake of H 2 TFPC-SMan is significantly higher than that of H 2 TFPC-SGlc at a concentration of 0.5¯M. These results are consistent with the experimental observation that the photocytotoxicity of H 2 TFPC-SMan is significantly higher than that of H 2 TFPC-SGlc in a concentration range from 0.2 to less than 1¯M.

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A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

Cited by 67 publications

References 46 publications

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

New photodynamic therapy with next-generation photosensitizers

Synthesis and Photophysical Properties of S-Mannosylated Chlorins and Their Effect on Photocytotoxicity in HeLa Cells

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