A Synergetic Approach Utilizing Nanotechnology, Chemotherapy, and Radiotherapy for Pancreatic Cancer Treatment

Abstract

The objective of this study was to assess the anticancer effectiveness of gold nanoparticles (GNPs) and lipid-encapsulated docetaxel prodrug (LNPDTX-P) with radiotherapy (RT). The study utilized a co-culture spheroid model comprising MIA PaCa-2 cancer cells and patient-derived cancer-associated fibroblasts (CAF-98) to mimic pancreatic cancer conditions. The spheroids underwent treatment with GNPs (7.5 μg/mL), LNPDTX-P (99 nM of DTX pro-drug), and 2 Gy of RT. Cell viability of the spheroids was evaluated using the CellTiter-Glo 3D assay. At the same time, DNA double-strand breaks (DSBs) were assessed by examining the expression of the DNA damage marker 53BP1 through an immunofluorescence assay. Alt-hough GNPs/RT and RT/LNPDTX-P showed a reduction in spheroid size and an apparent in-crease in DNA DSB damage, the combination of the two nanoparticles, GNPs, and LNPDTX-P, with RT, significantly enhanced the anticancer efficacy, resulting in a 28% decrease in spheroid size and an estimated 39% increase in DNA DSB. The combination of GNPs and LNPDTX-P with RT showed a synergetic effect due to their radiosensitizing properties, improving the ther-apeutic efficacy of each treatment modality alone. This triple modality offers a hopeful strategy to enhance cancer treatment efficacy while reducing adverse effects.