Antitumor Activity of Thermosensitive Hydrogels Packaging Gambogic Acid Nanoparticles and Tumor-Penetrating Peptide iRGD Against Gastric Cancer
Dinghu Zhang,1,2,* Yanhong Chu,1,* Hanqing Qian,1 Lingyu Qian,1 Jie Shao,1 Qiuping Xu,1 Lixia Yu,1 Rutian Li,1 Quanan Zhang,3 Fenglei Wu,4 Baorui Liu,1 Qin Liu1 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing Univ...
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| Autores principales: | , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2020
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/6d66528fa5be41eb9bcc783a25149dfb |
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| Sumario: | Dinghu Zhang,1,2,* Yanhong Chu,1,* Hanqing Qian,1 Lingyu Qian,1 Jie Shao,1 Qiuping Xu,1 Lixia Yu,1 Rutian Li,1 Quanan Zhang,3 Fenglei Wu,4 Baorui Liu,1 Qin Liu1 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 2Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China; 3Department of Oncology, Jiangning Hospital, Nanjing, People’s Republic of China; 4Department of Oncology, Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Liu; Baorui LiuThe Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing 210008, People’s Republic of ChinaTel +86-25-83107081Fax +86-25-83317016Email liuqinxh@126.com; baoruiliu@nju.edu.cnIntroduction: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity.Methods: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size.Results: The thermo-sensitive properties of hydrogels were characterized by 3– 4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased.Discussion: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.Keywords: gambogic acid, hydrogel, nanoparticles, iRGD, gastric cancer |
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