Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer

Abstract

Sneha Mahalunkar,1 Amit Singh Yadav,2 Mahadeo Gorain,2 Vinay Pawar,3,4 Ranveig Braathen,5,6 Siegfried Weiss,3 Bjarne Bogen,5,6 Suresh W Gosavi,7 Gopal C Kundu2 1School of Basic Medical Science, Savitribai Phule Pune University, Pune 411007, Maharashtra, India; 2Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, India; 3Institute of Immunology, Hannover Medical School, Hannover, Germany; 4Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany; 5K.G. Jebsen Centre for Influenza Vaccines Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 6Oslo University Hospital, Oslo 0027, Norway; 7Department of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaCorrespondence: Gopal C KunduLaboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, IndiaTel [phone]Fax [phone]Email [email protected] Suresh W GosaviDepartment of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaTel [phone]Fax [phone]Email [email protected]: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate–curcumin-loaded gold–polyvinylpyrrolidone nanoparticles (FA–CurAu-PVP NPs) for targeted delivery in breast cancer model systems.Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid–curcumin Au-PVP NCs (FA–CurAu-PVP NCs) were characterized by ultraviolet–visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model.Results: Curcumin (40 μg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA–CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3ʹ,5,5ʹ-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis.Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.Keywords: curcumin, gold nanoconjugate, folic acid, breast cancer cell line, cytotoxic activity

Keywords

• Curcumin
• gold nanoconjugate
• folic acid
• breast cancer cell line
• cytotoxic activity.