Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis
Abstract Background Pancreatic adenocarcinoma (PDAC) is one of the most fatal malignancies. Surgical resection supplemented by chemotherapy remains the major therapeutic regimen, but with unavoidable resistance and systemic toxic reaction. Curcumin is a known safe natural compound that can effective...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-020-00687-2 |
| _version_ | 1811187858943246336 |
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| author | Tao Cheng Zhiheng Zhang Hua Shen Ziying Jian Junsheng Li Yujun Chen Yi Shen Xinyi Dai |
| author_facet | Tao Cheng Zhiheng Zhang Hua Shen Ziying Jian Junsheng Li Yujun Chen Yi Shen Xinyi Dai |
| author_sort | Tao Cheng |
| collection | DOAJ |
| description | Abstract Background Pancreatic adenocarcinoma (PDAC) is one of the most fatal malignancies. Surgical resection supplemented by chemotherapy remains the major therapeutic regimen, but with unavoidable resistance and systemic toxic reaction. Curcumin is a known safe natural compound that can effectively eliminate pancreatic adenocarcinoma cells in vitro, making it a promising candidate for substitution in subsequent chemotherapy. However, due to its extremely low bioavailability caused by its insolubility and circular elimination, curcumin had an unexpectedly modest therapeutic effect in clinical trials. Results Here, we electrospun curcumin/gelatin-blended nanofibrous mat to largely improve curcumin’s bioavailability by local controlled-release. With characterization by scanning electron microscopy, fluorescence microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and high-performance liquid chromatography, it was revealed that curcumin was uniformly dispersed in the fiber of the mats with nanoscopic dimensions and could be continuously released into the surrounding medium for days. The cancer inhibitory effects of nano-curcumin and underlying mechanisms were further explored by assays using pancreatic adenocarcinoma cell and experiments using xenograft model. The results showed the released nano-curcumin could effectively inhibit pancreatic adenocarcinoma cell proliferation not only in vitro, but more importantly in vivo. This cytotoxic effect of nano-curcumin against pancreatic adenocarcinoma was achieved through provoking the production of intracellular reactive oxygen species and activating endoplasmic reticulum stress, which leads to enhanced cell apoptosis via decreased phosphorylation of signal transducer and activator of transcription 3. Conclusions Clinically, curcumin/gelatin-blended nanofibrous mat could be a promising, secure, efficient and affordable substitutional agent for the elimination of residual cancer cells after tumor resection. Moreover, our strategy to obtain curcumin released from nanofibrous mat may provide a universally applicable approach for the study of the therapeutic effects and molecular mechanisms of other potential medicines with low bioavailability. |
| first_indexed | 2024-04-11T14:10:42Z |
| format | Article |
| id | doaj.art-cb199a77dd1e4f788314fbabf6169365 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T14:10:42Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-cb199a77dd1e4f788314fbabf61693652022-12-22T04:19:44ZengBMCJournal of Nanobiotechnology1477-31552020-09-0118111210.1186/s12951-020-00687-2Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosisTao Cheng0Zhiheng Zhang1Hua Shen2Ziying Jian3Junsheng Li4Yujun Chen5Yi Shen6Xinyi Dai7Department of General Surgery, Zhongda Hospital, Medical School, Southeast UniversityDepartment of Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of MunichDepartment of Plastic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast UniversityDepartment of General Surgery, Zhongda Hospital, Medical School, Southeast UniversityBio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityBio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of MedicineAbstract Background Pancreatic adenocarcinoma (PDAC) is one of the most fatal malignancies. Surgical resection supplemented by chemotherapy remains the major therapeutic regimen, but with unavoidable resistance and systemic toxic reaction. Curcumin is a known safe natural compound that can effectively eliminate pancreatic adenocarcinoma cells in vitro, making it a promising candidate for substitution in subsequent chemotherapy. However, due to its extremely low bioavailability caused by its insolubility and circular elimination, curcumin had an unexpectedly modest therapeutic effect in clinical trials. Results Here, we electrospun curcumin/gelatin-blended nanofibrous mat to largely improve curcumin’s bioavailability by local controlled-release. With characterization by scanning electron microscopy, fluorescence microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and high-performance liquid chromatography, it was revealed that curcumin was uniformly dispersed in the fiber of the mats with nanoscopic dimensions and could be continuously released into the surrounding medium for days. The cancer inhibitory effects of nano-curcumin and underlying mechanisms were further explored by assays using pancreatic adenocarcinoma cell and experiments using xenograft model. The results showed the released nano-curcumin could effectively inhibit pancreatic adenocarcinoma cell proliferation not only in vitro, but more importantly in vivo. This cytotoxic effect of nano-curcumin against pancreatic adenocarcinoma was achieved through provoking the production of intracellular reactive oxygen species and activating endoplasmic reticulum stress, which leads to enhanced cell apoptosis via decreased phosphorylation of signal transducer and activator of transcription 3. Conclusions Clinically, curcumin/gelatin-blended nanofibrous mat could be a promising, secure, efficient and affordable substitutional agent for the elimination of residual cancer cells after tumor resection. Moreover, our strategy to obtain curcumin released from nanofibrous mat may provide a universally applicable approach for the study of the therapeutic effects and molecular mechanisms of other potential medicines with low bioavailability.http://link.springer.com/article/10.1186/s12951-020-00687-2CurcuminNanofibrous mat (NM)Pancreatic adenocarcinomaTumor suppressionBioavailability |
| spellingShingle | Tao Cheng Zhiheng Zhang Hua Shen Ziying Jian Junsheng Li Yujun Chen Yi Shen Xinyi Dai Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis Journal of Nanobiotechnology Curcumin Nanofibrous mat (NM) Pancreatic adenocarcinoma Tumor suppression Bioavailability |
| title | Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis |
| title_full | Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis |
| title_fullStr | Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis |
| title_full_unstemmed | Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis |
| title_short | Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis |
| title_sort | topically applicated curcumin gelatin blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ros production and endoplasmic reticulum stress mediated apoptosis |
| topic | Curcumin Nanofibrous mat (NM) Pancreatic adenocarcinoma Tumor suppression Bioavailability |
| url | http://link.springer.com/article/10.1186/s12951-020-00687-2 |
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