[Antitumor effects of redox-responsive nanoparticles containing platinumï¼â
£ï¼in ovarian cancer].
Zhonghua Zhong Liu Za Zhi
; 46(1): 76-85, 2024 Jan 23.
Article
em Zh
| MEDLINE
| ID: mdl-38246783
ABSTRACT
Objectives:
To explore the antitumor effects of redox-responsive nanoparticles containing platinum(â £)-NP@Pt(â £) in ovarian cancer.Methods:
Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(â £)-Pt(â £) can self-assemble into NP@Pt(â £). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(â £) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(â £) and NP@Pt(â £). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(â £) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(â £). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:
The platinum release of NP@Pt(â £) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(â £) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(â £) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, Pï¼0.05). The half inhibitory concentrations of NP@Pt(â £) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(â £) was (33.91±3.80)%, which was significantly higher than that of Pt(â £) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, Pï¼0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(â £) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(â £) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(â £) compared with cisplatin. The change in body weight of mice in NP@Pt(â £) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining.Conclusion:
Redox-responsive NP@Pt(â £), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Cistadenocarcinoma Seroso
Limite:
Animals
/
Female
/
Humans
Idioma:
Zh
Revista:
Zhonghua Zhong Liu Za Zhi
Ano de publicação:
2024
Tipo de documento:
Article