Antitumor effect of photodynamic therapy with a novel targeted photosensitizer on cervical carcinoma
| Autor: | Dong-Hong Li, Hua-Lang Xiao, Peng-Xi Li, Jiang-Hong Mu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Porphyrins medicine.medical_treatment Mice Nude Uterine Cervical Neoplasms Apoptosis Photodynamic therapy HeLa chemistry.chemical_compound In vivo medicine Animals Humans Tissue Distribution MTT assay Photosensitizer Mice Inbred BALB C Photosensitizing Agents biology General Medicine biology.organism_classification Xenograft Model Antitumor Assays Molecular biology Photochemotherapy Oncology chemistry Folate receptor Chlorin Female HeLa Cells |
| Zdroj: | Oncology Reports. 33:125-132 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2014.3593 |
| Popis: | The antitumor effect of photodynamic therapy (PDT) mediated by a novel photosensitizer I (Ps I; {γ-[N-poly(ethyleneglycol)]folic acid}-5,10,15-tris(3-hydroxyphenyl)-20-(4-carboxyphenyl)chlorin), in which chlorin was used as a photoactive unit, folic acid as a tumor‑targeting warhead, and polyethylene glycol as a linker, on cervical carcinoma was studied in vitro and in vivo. Ps I exhibited a considerably higher cellular uptake by HeLa cells than folic acid-free analogue Ps A (tert-butyl N-poly(ethyleneglycol)ethylcarbamate-5,10,15-tris(3-hydroxyphenyl)-20-(4-carboxyphenyl)chlorin), and the cellular uptake by HeLa cells of Ps I could be competitively inhibited by excess folic acid. Moreover, at different time points after the intravenous (i.v.) injection of Ps I and A, Ps I produced a >2-fold higher tumor to normal tissue ratio in tumor-bearing nude mice as compared to Ps A. MTT assay indicated that the HeLa cell proliferation inhibition ratio was increased 34% after Ps I-PDT compared with Ps A-PDT with a photosensitizer concentration of 15.2 µmol/l. Administration of Ps I (7 mg/kg, i.v.) followed by light exposure (80 J/cm2) markedly suppressed the growth of xenograft tumors, and the tumor volume was 10-fold smaller than that of the control group. Tumor growth inhibition in vitro and in vivo had an obvious dependency on the Ps I concentration and irradiation dose. The mode of cell death post-Ps I-PDT was analyzed by flow cytometry, confocal laser scanning microscopy, and electron microscope, and the results suggested that apoptosis was the primary mode of HeLa cell death induced by Ps I-PDT. The results also demonstrated that tumor targeting of Ps I was clearly improved because of the endocytosis mediated by the folate receptor. As a result, Ps I-PDT exhibited higher antitumor activity than Ps A-PDT and has potential as an alternative treatment modality for cervical cancer. |
| Databáze: | OpenAIRE |
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