Arginine-Glycine-Aspartic-Modified Silver Nanoparticles Improve the In Vitro Anti-Cancer Efficacy of Adriamycin for Prostate Cancer Treatment

Abstract

Prostate cancer (PC) is the most frequently diagnosed cancer in men and it is difficult to achieve the desired therapeutic effect through traditional chemotherapy. Thus, it is necessary to develop advanced strategies to treat PC. Functionalized nanoparticles have been developed as a unique tumor-targeted delivery platform for PC therapy. In this study, tumor-targeted RGD-silver nanoparticles (RGD-Ag NPs) were prepared, in which RGD could specially bind with its receptor αvβ3 integrin over-expressed on LNCaP cells. RGD-Ag NPs were adopted to load adriamycin (Am) to prepare functionalized silver nanoparticles (RGD-Ag@Am). The average particle size of RGD-Ag@Am was about 65 nm and kept under 90 nm during the 8-day trial period. LNCaP cells showed greater uptake in RGD-Ag@Am group compared to Ag@Am group, indicating active targeting of carrier RGD-Ag NPs could effectively enhance the uptake of Am in LNCaP cells. RGD-Ag@Am entered LNCaP cells in a clathrin-mediated energy-dependent manner and demonstrated an excellent pH-response release of Am under the acidic condition, which was conducive to enhancing the distribution of Am in the tumor microenvironment. RGD-Ag@Am inhibited the proliferation and invasion of LNCaP cells and induced LNCaP cell apoptosis which probably promotes the production of reactive oxygen species (ROS). It was noteworthy that RGD-Ag@Am exhibited greater anti-cancer activity in comparison with free Am and Ag@Am in the LNCaP cell model, indicating that RGD-Ag NPs had the ability to enhance the anti-cancer efficacy of Am. These findings showed that RGD-Ag@Am has promising potential for use in PC therapy.