hypocrellin-b and Ovarian-Neoplasms

Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active-targeting, water-soluble and pharmacomodulated photosensitizer nanocarrier. Drug-loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA-PEG-PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA-PEG-PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR-). The enhanced uptake of HB/FA-PEG-PLA micelles to cancer cells resulted in a more effective post-PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA-PEG-PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate-targeted micelles in tumor-bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20-fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB-loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA-PEG-PLA micelles have a high drug-loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

Topics: Animals; Cell Line, Tumor; Drug Carriers; Drug Liberation; Female; Folic Acid; Humans; Mice, Nude; Micelles; Ovarian Neoplasms; Perylene; Photosensitizing Agents; Polyesters; Polyethylene Glycols; Polymers; Quinones; Rats, Sprague-Dawley; Tissue Distribution; Xenograft Model Antitumor Assays

Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ascites model using Fischer 344 rats and PBCA-NP entrapped with HB (HB-PBCA-NP) were formed successfully. The pharmacodynamic characteristics and biodistribution of the HB-PBCA-NP system were evaluated by comparison with HB dimethyl sulfoxide (HB-DMSO) and testing at various time-points following intraperitoneal drug administration. HB-PBCA-NP-based PDT combined with cytoreductive surgery was then administrated to the tumor-bearing animals. Kaplan-Meier survival analysis was performed to assess the therapeutic effect of the nanoparticle system. The serum HB concentration peaked 4 h after drug administration in the nanoparticle system, and 1 h with HB-DMSO. The peak exposure time of tumor tissues was also extended (4 vs. 2 h), and PBCA-NP remained present for much longer than HB-DMSO. Although PDT combined with surgery prolonged the survival time significantly compared with surgery alone (84 days, P<0.05), there was no significant difference in the survival time of animals that received either HB-PBCA-NP- or HB-DMSO-based PDT after cytoreductive surgery (99 vs. 95 days, P=0.293). PBCA-NP exhibited potential advantages in controlled drug release and tumor targeting, which was beneficial for HB-based PDT. PDT combined with surgery prolonged the survival time, suggesting that this might be an alternative treatment option for ovarian cancer.

Topics: Animals; Cell Line, Tumor; Combined Modality Therapy; Dimethyl Sulfoxide; Enbucrilate; Female; Injections, Intraperitoneal; Nanoparticles; Ovarian Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Quinones; Rats; Tissue Distribution; Treatment Outcome

In the present study, we investigated effects of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells in vitro.. Human ovarian cancer HO-8910 cell as a cancer model cell was incubated with hypocrellin B at a concentration of 2.5 μM for 5 h and irradiated by light from a light-emitting diodes (LED) source. Cell apoptosis was analyzed by flow cytometry with annexin V/propidium iodide (PI) staining and nuclear staining 6 h after hypocrellin B photoirradiation. Cell adhesion was assessed using the 3-(4, 5-dimthylthiazol-2-yl)-2, 5 diphenyl-tetrazolium bromide (MTT) assay 4 h after photodynamic treatment. Cell migration was measured 48 h after photodynamic treatment.. Flow cytometry with annexin V/PI staining showed that early apoptotic and late apoptotic (necrotic) rates following photodynamic therapy with hypocrellin B markedly increased to 16.40% and 24.67%, respectively. Nuclear staining found nuclear condensation and typical apoptotic body in the treated cells. The number of cell migration was significantly decreased to 183 ± 28 after photodynamic therapy with hypocrellin B (p < 0.01). Light irradiation alone and hypocrellin B alone had no significant effect on cell migration. The cell adhesion inhibitory rate due to photodynamic action of hypocrellin B was 53.2 ± 1.8%, significantly higher than 2.7 ± 2.1% of light treatment alone and 1.0 ± 0.4% of hypocrellin B treatment alone (p < 0.01).. The findings demonstrated that photodynamic therapy with hypocrellin B remarkably induced apoptosis and inhibited adhesion and migration of cancer cells in vitro.

Topics: Apoptosis; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Nucleus; Female; Humans; Ovarian Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Quinones

Photodynamic therapy (PDT) is considered a promising new strategy for ovarian cancer treatment. As the key component in PDT, photosensitizer metabolism and localization in cancer cells is particularly important.. The localization of the photosensitizers hematoporphyrin monomethyl ether (HMME) and hypocrellin B (HB) were determined in the ovarian cancer cell lines SKOV3 and NuTu-19 by fluorescence microscopy and laser scanning confocal microscopy(LSCM). A JD801 image analysis system was used to analyze the fluorescence intensity of the photosensitizers in the cells. The phototoxicity of both drugs to the cancer cells was determined by MTT assay.. Both photosensitizers were mainly distributed in the cytoplasm. Drug uptake reached a peak after 4 h incubation with HB and after 3 h incubation with HMME. Within a certain range, the higher the concentration, the stronger the fluorescence became and at 40 μg/ml, the intracellular photosensitizer had reached saturation. Based on these results PDT was applied to SKOV3 cells. All the cells were killed when the photosensizer dose reached 40 μg/ml.. PDT is an effective therapy for ovarian cancer cells.

Topics: Cell Line, Tumor; Female; Hematoporphyrins; Humans; Imaging, Three-Dimensional; Intracellular Space; Light; Microscopy, Confocal; Microscopy, Fluorescence; Ovarian Neoplasms; Perylene; Quinones; Subcellular Fractions; Time Factors