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

Journal of Nanobiotechnology

Yujun Chen¹  Yi Shen¹  Tao Cheng²  Junsheng Li²  Ziying Jian³  Hua Shen⁴  Xinyi Dai⁵  Zhiheng Zhang⁶ 

[1] Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University;Department of General Surgery, Zhongda Hospital, Medical School, Southeast University;Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University;Department of Plastic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine;Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine;Department of Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich;

关键词: Curcumin;    Nanofibrous mat (NM);    Pancreatic adenocarcinoma;    Tumor suppression;    Bioavailability;   

DOI  :  10.1186/s12951-020-00687-2

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown