International Journal of Nanomedicine (Nov 2016)
Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO2; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO2 nanoparticles
Abstract
Lingling Ding,1–3 Jiawei Li,1,2 Rui Huang,1,2 Zhidong Liu,1,2 Chunhua Li,1–3 Shaozi Yao,1,2 Jinyan Wang,1,2 Dongli Qi,1,2 Nan Li,1,2 Jiaxin Pi1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Tianjin University of Traditional Chinese Medicine, 3Tianjin International Joint Academy of Biomedicine, Tianjin, People’s Republic of ChinaAbstract: Targeted delivery by the folate ligand is an effective way to enhance an anti-breast carcinoma effect, due to its high affinity for the folate receptor, which is overexpressed in many tumor cells. In this study, we firstly synthesized a folic acid (FA)-targeted and polyethylene glycol (PEG)-modified TiO2 nanocarrier. Then, an FA-PEG-TiO2 nanoparticle (NP) codelivery system loaded with curcumin and salvianolic acid B were prepared by emulsion evaporation–solidification at low temperature. The obtained folate-targeted NPs (FA-NPs) showed more cytotoxicity on MCF7 cells and MDA-MB-231 cells than a nontargeted NP group. Apart from a synergistic anti-breast cancer effect with curcumin, salvianolic acid B protects the cardiovascular system from oxidative injury by the TiO2 nanocarrier. With coumarin 6 as a fluorescent probe to observe cellular uptake of NPs, the results of in vitro cellular uptake demonstrated FA-NPs exhibited higher cellular uptake and accumulation in MCF7 cells and MDA-MB-231 cells than nontargeted NPs. Then, in vivo biodistribution of NPs was further qualitatively and quantitatively confirmed by in vivo imaging. More importantly, the animal study further suggested that FA-NPs had significantly stronger antitumor effects via receptor-mediated targeted delivery. Consequently, FA-PEG-TiO2 NPs loaded with curcumin and salvianolic acid B could be a promising drug-delivery system to treat breast cancer. Keywords: breast cancer, codelivery, curcumin, FA-PEG-TiO2, nanoparticles, salvianolic acid B