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

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

Supplementary material

Figure S1 Cell viability of blank NPs, Sol, NPs, and FA-NPs on MCF7 cells and MDA-MB-231 cells.

Notes: *P<0.05; **P<0.01; ***P<0.001. Data presented as means ± standard deviation (n=3). (A) Cell viability of blank NPs on MCF7 cells; (B) cell viability of blank NPs on MDA-MB-231 cells; (C) cell viability of Sol, NPs, and FA-NPs incubating MCF7 cells for 24 hours; (D) cell viability of Sol, NPs, and FA-NPs incubating MCF7 cells for 48 hours; (E) cell viability of Sol, NPs, and FA-NPs incubating MDA-MB-231 cells for 24 hours; (F) cell viability of Sol, NPs, and FA-NPs incubating MDA-MB-231 cells for 48 hours.

Abbreviations: NPs, nanoparticles; Sol, solution (free Cur-Sal); FA, folic acid; Cur, curcumin; Sal, salvianolic acid.

Acknowledgments

We thank Dr Jiawei Li and Dr Zhidong Liu for their substantial contributions to concepts and design. Meanwhile, we appreciate Weibing Duan and Qian Zhang for their help on the animal experiments. We express our gratitude to Dr Xinggang Yang who offered us MCF7 cells from Shenyang Pharmaceutical University. This study was financially supported by the Program for The Research Plan of Application Foundation and Frontier Technology in Tianjin (Natural Science Funds) (16JCYBJC282000).

Disclosure

The authors report no conflicts of interest in this work.