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Bioluminescence-activated deep-tissue photodynamic therapy of cancer.

Kim YR, Kim S, Choi JW, Choi SY, Lee SH, Kim H, Hahn SK, Koh GY, Yun SH - Theranostics (2015)

Bottom Line: Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited.For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s.Our results show the promising potential of novel bioluminescence-activated PDT.

View Article: PubMed Central - PubMed

Affiliation: 1. Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 3. Department of Oncology, Asan Medical Center, Univ. Ulsan College of Medicine, Seoul , Korea.

ABSTRACT
Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.

No MeSH data available.


Related in: MedlinePlus

Therapeutic effects of LN BL-PDT on animal survival and lung metastasis. a. Kaplan-Meier survival curve of CT26 bearing mice. b. H&E stained images of lung harvested 14 days after LN PDT. Arrows indicate small nodules in treated mice (top) and larger nodules with the sign of metastatic infiltration (bottom). Scale bar, 1 mm. c. The total number of metastatic lung nodules found from each animal group (6 lung sections per mouse, 12 mice). d. Kaplan-Meier survival curve of LLC-GFP bearing mice. e. Photographs of the lungs harvested at day 25. Circles indicate macroscopic metastatic nodules. f. The numbers of lung surface metastases. g. The weights of the lungs. *, Kruskal-Wallis test p <0.05; **, p <0.01.
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Figure 7: Therapeutic effects of LN BL-PDT on animal survival and lung metastasis. a. Kaplan-Meier survival curve of CT26 bearing mice. b. H&E stained images of lung harvested 14 days after LN PDT. Arrows indicate small nodules in treated mice (top) and larger nodules with the sign of metastatic infiltration (bottom). Scale bar, 1 mm. c. The total number of metastatic lung nodules found from each animal group (6 lung sections per mouse, 12 mice). d. Kaplan-Meier survival curve of LLC-GFP bearing mice. e. Photographs of the lungs harvested at day 25. Circles indicate macroscopic metastatic nodules. f. The numbers of lung surface metastases. g. The weights of the lungs. *, Kruskal-Wallis test p <0.05; **, p <0.01.

Mentions: To assess the effects of the LN treatment on distant metastasis, the lungs from treated (n=13) and untreated (n=12) animals were harvested 25 days after implantation of CT26 cells and 14 days after LN BL-PDT. Four mice of the untreated group died by day 25, where as 100% of the treated mice survived (Fig. 7a). The increase of survival time for the treated animals was statistically significant. Histology of the lung tissues showed that the metastatic lung nodules in the treated mice were substantially smaller than those in the untreated survived mice (Fig. 7b). The number of lung nodules was significantly smaller in the treated group (Fig. 7c). We also performed the same experiment with LLC bearing mice in a treated (n=10) and untreated (n=10) groups. By day 25, 3 untreated mice died whereas none died from the treated group (Fig. 7d). The apparent size of the tumor nodules in the surface of the lung was significantly less in the treated animals (Fig. 7e and Supplementary Fig. 13). The number of visible metastasis in the lung surface was less in the treated mice (Fig. 7f). The weight of the lung was also smaller in the treated mice (Fig. 7g). These results indicate that LN PDT effectively reduced distant lung metastasis and extended the survival time of tumor-bearing animals.


Bioluminescence-activated deep-tissue photodynamic therapy of cancer.

Kim YR, Kim S, Choi JW, Choi SY, Lee SH, Kim H, Hahn SK, Koh GY, Yun SH - Theranostics (2015)

Therapeutic effects of LN BL-PDT on animal survival and lung metastasis. a. Kaplan-Meier survival curve of CT26 bearing mice. b. H&E stained images of lung harvested 14 days after LN PDT. Arrows indicate small nodules in treated mice (top) and larger nodules with the sign of metastatic infiltration (bottom). Scale bar, 1 mm. c. The total number of metastatic lung nodules found from each animal group (6 lung sections per mouse, 12 mice). d. Kaplan-Meier survival curve of LLC-GFP bearing mice. e. Photographs of the lungs harvested at day 25. Circles indicate macroscopic metastatic nodules. f. The numbers of lung surface metastases. g. The weights of the lungs. *, Kruskal-Wallis test p <0.05; **, p <0.01.
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Related In: Results  -  Collection

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Figure 7: Therapeutic effects of LN BL-PDT on animal survival and lung metastasis. a. Kaplan-Meier survival curve of CT26 bearing mice. b. H&E stained images of lung harvested 14 days after LN PDT. Arrows indicate small nodules in treated mice (top) and larger nodules with the sign of metastatic infiltration (bottom). Scale bar, 1 mm. c. The total number of metastatic lung nodules found from each animal group (6 lung sections per mouse, 12 mice). d. Kaplan-Meier survival curve of LLC-GFP bearing mice. e. Photographs of the lungs harvested at day 25. Circles indicate macroscopic metastatic nodules. f. The numbers of lung surface metastases. g. The weights of the lungs. *, Kruskal-Wallis test p <0.05; **, p <0.01.
Mentions: To assess the effects of the LN treatment on distant metastasis, the lungs from treated (n=13) and untreated (n=12) animals were harvested 25 days after implantation of CT26 cells and 14 days after LN BL-PDT. Four mice of the untreated group died by day 25, where as 100% of the treated mice survived (Fig. 7a). The increase of survival time for the treated animals was statistically significant. Histology of the lung tissues showed that the metastatic lung nodules in the treated mice were substantially smaller than those in the untreated survived mice (Fig. 7b). The number of lung nodules was significantly smaller in the treated group (Fig. 7c). We also performed the same experiment with LLC bearing mice in a treated (n=10) and untreated (n=10) groups. By day 25, 3 untreated mice died whereas none died from the treated group (Fig. 7d). The apparent size of the tumor nodules in the surface of the lung was significantly less in the treated animals (Fig. 7e and Supplementary Fig. 13). The number of visible metastasis in the lung surface was less in the treated mice (Fig. 7f). The weight of the lung was also smaller in the treated mice (Fig. 7g). These results indicate that LN PDT effectively reduced distant lung metastasis and extended the survival time of tumor-bearing animals.

Bottom Line: Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited.For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s.Our results show the promising potential of novel bioluminescence-activated PDT.

View Article: PubMed Central - PubMed

Affiliation: 1. Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 3. Department of Oncology, Asan Medical Center, Univ. Ulsan College of Medicine, Seoul , Korea.

ABSTRACT
Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.

No MeSH data available.


Related in: MedlinePlus