Development of Functionalized Gold Nanoparticles for Safe and Efficient Delivery of Methotrexate Sodium in Breast Cancer

Abstract

Currently, gold nanoparticles (AuNPs) are widely used for medical applications as drug carriers, a therapeutic agent and a diagnostic agent due to their small size and surface plasmon resonance property. In this research work, AuNPs were synthesized by the chemical reduction method using various effective reducing agents. Trisodium citrate was found as an efficient reducing agent for the synthesis of small size AuNPs. However, trisodium citrate was not able to produce stable AuNPs. Thus, further AuNPs were stabilized using tween 80 as a co-reducing and stabilizing agent. With an increasing concentration of tween 80, a decrease in the size of produced AuNPs was observed, along with a significant decrease in the size distribution. Herein, Methotrexate sodium, an effective anticancer drug loaded onto the surface of stabilized AuNPs for the delivery of breast cancer. Present work also developed the PLGA conjugated AuNPs for the controlled release of the drug loaded on the surface of AuNPs. Besides, they also provide the stabilization of AuNPs dispersion. Hydrodynamic diameter and zeta potential of PLGA conjugated drug loaded AuNPs were confirmed as 100.3 nm and negative charge respectively. In the present study, we also prepared hyaluronic acid (HA) conjugated Methotrexate sodium loaded gold nanoparticles to selectively deliver a drug into a breast cancer tumor as the HA targets tumor cells via specific interaction of the HA polymer with the CD44 receptor. Prepared hyaluronic acid conjugated AuNPs were found to have a mean hydrodynamic diameter of approximately 81.75 nm and negative zeta potential. Furthermore, transmission electron microscopy showed the clear conjugation layer of both polymers PLGA and HA on functionalized AuNPs. The AuNPs functionalized with PLGA and with HA showed greater cytotoxicity and cellular uptake than only Methotrexate sodium loaded AuNPs. Moreover, MTX loaded formulations could arrest the cells in the G1-S phase confirming the mechanism of action of MTX on the S phase.