Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS produ
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Journal of Nanobiotechnology Open Access
RESEARCH
Topically applicated curcumin/ gelatin‑blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis Tao Cheng1†, Zhiheng Zhang2†, Hua Shen3, Ziying Jian4, Junsheng Li1, Yujun Chen5, Yi Shen5* and Xinyi Dai6*
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
*Correspondence: [email protected]; [email protected] † Tao Cheng and Zhiheng Zhang contributed equally to this work 5 Bio‑ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China 6 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to t
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