scholarly journals Self-luminescent photodynamic therapy using breast cancer targeted proteins

2020 ◽  
Vol 6 (37) ◽  
pp. eaba3009
Author(s):  
Eun Hye Kim ◽  
Sangwoo Park ◽  
Yun Kyu Kim ◽  
Minwoo Moon ◽  
Jeongwon Park ◽  
...  

Despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the nondegradable risks of photosensitizing drugs and limits of light penetration and instrumentation. Here, we present bioluminescence (BL)–induced proteinaceous PDT (BLiP-PDT), through the combination of luciferase and a reactive oxygen species (ROS)–generating protein (Luc-RGP), which is self-luminescent and degradable. After exposure to coelenterazine-h as a substrate for luciferase without external light irradiation, Luc-RGP fused with a small lead peptide–induced breast cancer cell death through the generation of BL-sensitive ROS in the plasma membrane. Even with extremely low light energy, BLiP-PDT exhibited targeted effects in primary breast cancer cells from patients and in in vivo tumor xenograft mouse models. These findings suggest that BLiP-PDT is immediately useful as a promising theranostic approach against various cancers.

2019 ◽  
Author(s):  
Liyi Huang ◽  
Haidan Lin ◽  
Qing Chen ◽  
Lehua Yu ◽  
dingqun bai

Abstract Abstract Background: Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells. Methods: Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining. Results: Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced and destroyed the F-actin cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion: Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis. Key words: photodynamic therapy, reactive oxygen species, breast tumor, migration, invasion


2019 ◽  
Vol 20 (5) ◽  
pp. 1148 ◽  
Author(s):  
Chun-Chen Yang ◽  
Wei-Yun Wang ◽  
Feng-Huei Lin ◽  
Chun-Han Hou

Conventional photodynamic therapy (PDT) is limited by its penetration depth due to the photosensitizer and light source. In this study, we developed X-ray induced photodynamic therapy that applied X-ray as the light source to activate Ce-doped CaCO3 (CaCO3:Ce) to generate an intracellular reactive oxygen species (ROS) for killing cancer cells. The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-induced CaCO3:Ce. The cell viability significantly decreased and cell cytotoxicity obviously increased with CaCO3:Ce exposure under X-ray irradiation, which is less harmful than radiotherapy in tumor treatment. CaCO3:Ce produced significant ROS under X-ray irradiation and promoted A549 cancer cell death. CaCO3:Ce can enhance the efficacy of X-ray induced PDT, and tumor growth was inhibited in vivo. The blood analysis and hematoxylin and eosin stain (H&E) stain fully supported the safety of the treatment. The mechanisms underlying ROS and CO2 generation by CaCO3:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed. These findings and advances are of great importance in providing a novel therapeutic approach as an alternative tumor treatment.


2014 ◽  
Vol 13 (12) ◽  
pp. 1793-1803 ◽  
Author(s):  
Xiaolan Feng ◽  
Yi Zhang ◽  
Pan Wang ◽  
Quanhong Liu ◽  
Xiaobing Wang

Glycolytic inhibitors can synergistically enhance the photosensitivity of breast cancer cells by triggering cellular mitochondria- and caspase-dependent cell apoptosis, which was induced by additional ROS generation in combination therapy.


2010 ◽  
Vol 49 ◽  
pp. S92-S93
Author(s):  
Paula Seixas Costa ◽  
Danielly Cristiny Ferraz Costa ◽  
Fabiana Alves Casanova ◽  
Jerson Lima Silva ◽  
Eliane Fialho Oliveira

2013 ◽  
Vol 33 (2) ◽  
pp. 423-430 ◽  
Author(s):  
LI-HUA LIU ◽  
YING-JUN ZHOU ◽  
LAN DING ◽  
SHUN-ZHI ZHANG ◽  
JI SUN ◽  
...  

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