Tumor selective uptake of drug-nanodiamond complexes improves therapeutic outcome in pancreatic cancer

Publication date: Available online 6 March 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Vijay S. Madamsetty, Anil Sharma, Maria Toma, Stefanie Samaniego, Audrey Gallud, Enfeng Wang, Krishnendu Pal, Debabrata Mukhopadhyay, Bengt FadeelAbstractPancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths and novel treatment approaches are urgently needed. Here we show that poly(ethylene glycol)-functionalized nanodiamonds loaded with doxorubicin (ND-PEG-DOX) afforded a considerable improvement over free drug in an orthotopic pancreatic xenograft model. ND-PEG-DOX complexes were also superior to free DOX in 3-dimensional (3D) tumor spheroids of PDAC. ND-PEG showed no cytotoxicity towards macrophages, and histopathological analysis showed no abnormalities of major organs upon in vivo administration of ND-PEG-DOX. These results provide evidence that ND-mediated drug delivery may serve as a means of improving the therapeutic outcome in PDAC.Graphical AbstractWe investigated the therapeutic potential of poly(ethylene glycol)-functionalized nanodiamonds (NDs) loaded with doxorubicin (ND-PEG-DOX) using an array of in vitro and in vivo models of pancreatic ductal adenocarcinoma (PDAC). Our results showed that ND-PEG-DOX were more effective than free drug in 3D models of PDAC, but not when cells were grown in 2D. We also demonstrated tumor-selective uptake of ND-PEG-DOX in vivo and we documented a superior antitumor activity wh...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research