Co-delivery of curcumin and resveratrol by folic acid-conjugated poly(glycerol adipate) nanoparticles for enhanced synergistic anticancer effect against osteosarcoma
Amaraporn Wongrakpanich, Huong Bui Thi Thu, Krisada Sakchaisri, Vincenzo Taresco, Valentina Cuzzucoli Crucitti, Somnuk Bunsupa, Jiraphong Suksiriworapong
Abstract
This study explored the co-delivery of curcumin (CUR) and resveratrol (RV) using folic acid-conjugated poly(glycerol adipate)-based nanoparticles (FPPC NPs) to enhance their synergistic anticancer effects against osteosarcoma. Based on synergistic toxicity experiments against Saos-2 cells, the optimal synergistic CUR:RV ratios were 1:2 and 1:3, which were used for co-encapsulation. Increasing the amount of RV in the co-loaded NPs did not affect the properties of the nanocarriers, but predominantly increased the loading capacity of RV, especially at the 1:3 ratio, by 1.8–2.0 times, mediated by their interaction. All co-loaded NPs demonstrated sustained release of CUR with a burst release of RV, and the presence of RV accelerated the initial release of CUR from the carriers. Furthermore, the co-encapsulated NPs maintained CUR and RV synergism and greatly enhanced their toxicity against osteosarcoma by at least 1.8 times compared to their corresponding solutions through profound accumulation of Saos-2 cells in the sub G1 phase and late apoptosis. The internalization of FPPC NPs into cells via endocytosis was dose- and time-dependent. This study offers a proof-of-concept for a potential co-delivery system using tumor-targeted poly(glycerol adipate)-based NPs to enhance the anticancer activity of CUR and RV against osteosarcoma.