Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer

Abstract

Danny Jian Hang Tng,1,* Peiyi Song,1,* Guimiao Lin,2,3,* Alana Mauluidy Soehartono,1 Guang Yang,1 Chengbin Yang,1 Feng Yin,1 Cher Heng Tan,4 Ken-Tye Yong1 1School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore; 2The Engineering Lab of Synthetic Biology, 3Research Institute of Uropoiesis and Reproduction, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore *These authors contributed equally to this work Abstract: In this study, multifunctional hybrid-polymeric nanoparticles were prepared for the treatment of cultured multicellular tumor spheroids (MCTS) of the PANC-1 and MIA PaCa-2 pancreatic carcinoma cell lines. To synthesize the hybrid-polymeric nanoparticles, the poly lactic-co-glycolic acid core of the particles was loaded with Rhodamine 6G dye and the chemotherapeutic agent, Paclitaxel, was incorporated into the outer phospholipid layer. The surface of the nanoparticles was coated with gadolinium chelates for magnetic resonance imaging applications. This engineered nanoparticle formulation was found to be suitable for use in guided imaging therapy. Specifically, we investigated the size-dependent therapeutic response and the uptake of nanoparticles that were 65 nm, 85 nm, and 110 nm in size in the MCTS of the two pancreatic cancer cell lines used. After 24 hours of treatment, the MCTS of both PANC-1 and MIA PaCa-2 cell lines showed an average increase in the uptake of 18.4% for both 65 nm and 85 nm nanoparticles and 24.8% for 110 nm nanoparticles. Furthermore, the studies on therapeutic effects showed that particle size had a slight influence on the overall effectiveness of the formulation. In the MCTS of the MIA PaCa-2 cell line, 65 nm nanoparticles were found to produce the greatest therapeutic effect, whereas 12.8% of cells were apoptotic of which 11.4% of cells were apoptotic for 85 nm nanoparticles and 9.79% for 110 nm nanoparticles. Finally, the study conducted in vivo revealed the importance of nanoparticle size selection for the effective delivery of drug formulations to the tumors. In agreement with our in vitro results, excellent uptake and retention were found in the tumors of MIA PaCa-2 tumor-bearing mice treated with 110 nm nanoparticles. Keywords: nanoparticles, individualized, cancer, multicellular tumor spheroids, hybrid-polymeric