A study on the mechanism of 5-aminolevulinic acid photodynamic therapy in vitro and in vivo in cervical cancer

Photodynamic therapy (PDT) is a promising treatment for cancer that has been recently accepted in the clinic. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Photodithazine, on cervical cancer model. When human papillomavirus type 16 (HPV16)- transformed mouse TC-1 cells were exposed to varied doses of Photodithazine with light irradiation (6.25 J/cm2), the significant growth inhibition of TC-1 cells was observed at 0.75 μg/mL of Photodithazine. The damaged cells by Photodithazine/PDT were categorized to be early and late apoptosis, as determined by annexin V staining. Photodithazine was primarily localized at lysosome apparatus within TC-1 cells while it was rapidly accumulated and sustained for initial 3 h in tumor tissue of TC-1 tumor bearing mice after IV injection. The tumor growth inhibition by Photodithazine/PDT with light irradiation (300 J/cm2) was examined after injection of various concentration of Photodithazine in tumor mice system. Our results show that Photodithazine/PDT might have significant advantages in the selective killing of tumor lesions in HPV 16 E6/E7 associated cervical cancer model, both in vitro and in vivo.

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Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage

Cells ◽

10.3390/cells10092190 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2190

Author(s):

Howard Kim ◽

Mi Woon Kim ◽

Young-IL Jeong ◽

Hoe Saeng Yang

Keyword(s):

Cervical Cancer ◽

Photodynamic Therapy ◽

Hela Cells ◽

Folate Receptor ◽

Chlorin E6 ◽

Ros Generation ◽

Cervical Cancer Cells ◽

Poly Ethylene

The aim of this study was to fabricate a reactive oxygen species (ROS)-sensitive and folate-receptor-targeted nanophotosensitizer for the efficient photodynamic therapy (PDT) of cervical carcinoma cells. Chlorin e6 (Ce6) as a model photosensitizer was conjugated with succinyl β-cyclodextrin via selenocystamine linkages. Folic acid (FA)-poly(ethylene glycol) (PEG) (FA-PEG) conjugates were attached to these conjugates and then FA-PEG-succinyl β-cyclodextrin-selenocystamine-Ce6 (FAPEGbCDseseCe6) conjugates were synthesized. Nanophotosensitizers of FaPEGbCDseseCe6 conjugates were fabricated using dialysis membrane. Nanophotosensitizers showed spherical shapes with small particle sizes. They were disintegrated in the presence of hydrogen peroxide (H2O2) and particle size distribution changed from monomodal distribution pattern to multimodal pattern. The fluorescence intensity and Ce6 release rate also increased due to the increase in H2O2 concentration, indicating that the nanophotosensitizers displayed ROS sensitivity. The Ce6 uptake ratio, ROS generation and cell cytotoxicity of the nanophotosensitizers were significantly higher than those of the Ce6 itself against HeLa cells in vitro. Furthermore, the nanophotosensitizers showed folate-receptor-specific delivery capacity and phototoxicity. The intracellular delivery of nanophotosensitizers was inhibited by folate receptor blocking, indicating that they have folate-receptor specificity in vitro and in vivo. Nanophotosensitizers showed higher efficiency in inhibition of tumor growth of HeLa cells in vivo compared to Ce6 alone. These results show that nanophotosensitizers of FaPEGbCDseseCe6 conjugates are promising candidates as PDT of cervical cancer.

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Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo

Journal of Cancer ◽

10.7150/jca.30690 ◽

2019 ◽

Vol 10 (17) ◽

pp. 4114-4122 ◽

Cited By ~ 6

Author(s):

Guifang He ◽

Tianlong Mu ◽

Yali Yuan ◽

Wenyan Yang ◽

Yuan Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Photodynamic Therapy ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway

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Sonodynamic and sono-photodynamic therapy in oncology

Biomedical Photonics ◽

10.24931/2413-9432-2019-8-2-31-46 ◽

2019 ◽

Vol 8 (2) ◽

pp. 31-46

Author(s):

D. A. Tzerkovsky ◽

E. L. Protopovich ◽

D. S. Stupak

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Pulse Frequency ◽

Antitumor Efficacy ◽

In Vivo Studies ◽

Malignant Neoplasms ◽

Serious Adverse Events ◽

Treatment Methods

In the present publication, authors have analyzed the results of using sonodynamic and sono-photodynamic therapy with photosensitizing agents of various classes (hematoporphyrin, 5-aminolevulinic acid, chlorin derivatives, etc.) in experimental oncology. In a number of in vitro and in vivo studies, the high antitumor efficacy of the above treatment methods has been proven. Ultrasonic treatment with a pulse frequency of 1–3 MHz and an intensity of 0.7 to 5 W/cm2 , independently and in combination with photo-irradiation of experimental tumors, can significantly improve the cytotoxic properties of photosensitizers. This became the basisfor testing the methodsin patients with malignant neoplasms of various localizations. Scientists fromSouth-East Asia presented the preliminary results of the use of sonodynamic and sono-photodynamic therapy with photosensitizers in the treatment of malignant pathology of the mammary gland, stomach, esophagus, prostate, lung and brain. Analysis of the obtained data indicates the absence of serious adverse events and an increase in the antitumor efficacy of treatment, which included these treatment methods with chlorin-type photosensitizers.

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