Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis

• Published in: Journal of nanobiotechnology 2020-09, Vol.18 (1), p.126-12, Article 126
• Main Authors: Cheng, Tao, Zhang, Zhiheng, Shen, Hua, Jian, Ziying, Li, Junsheng, Chen, Yujun, Shen, Yi, Dai, Xinyi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Analysis; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Bioavailability; Biocompatibility; Biological Availability; Cancer; Cancer prevention; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; Clinical trials; Controlled release; Curcumin; Curcumin - pharmacology; Cytotoxicity; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Fluorescence; Fluorescence microscopy; Fourier transforms; Gelatin; Gelatin - pharmacology; Health aspects; High performance liquid chromatography; Humans; Immunotherapy; Infrared spectroscopy; Liquid chromatography; Mats; Mice; Microscopy; Molecular modelling; Nanofibers - chemistry; Nanofibrous mat (NM); Pancreas; Pancreatic adenocarcinoma; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Phosphorylation; Radiation therapy; Reactive oxygen species; Reactive Oxygen Species - metabolism; Scanning electron microscopy; Substitution reactions; Surgery; Surgical equipment; Transcription; Tumor removal; Tumor suppression; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-020-00687-2

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. 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. 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.