Functionalized Silver Nanoparticles Enhance Therapeutic Effect of Paclitaxel for Prostate Cancer Therapy by Arresting the Cellular Cycle and Producing ROS

Chemotherapy has been proven to be an efficient strategy for the treatment of prostate cancer (PC). However, the insufficient cellular uptake of drugs is the biggest challenge for PC therapy. Therefore, in order to address the above concern, we developed tumor-targeted hyaluronic acid-silver nanoparticles (HA-Ag NPs), in which hyaluronic acid can specially bind with its receptor CD44 overexpressed on LNCaP cells. HA-Ag NPs have been used to load paclitaxel (PTX) to prepare functionalized silver nanoparticles (HA-Ag-PTX). The average particle size of HA-AgPTX was about 70 nm and kept under 120 nm for eight days. androgen-sensitive prostate cancer cells (LNCaP) cells show good uptake of HA-Ag-PTX, and HA-Ag-PTX enters LNCaP cells in a clathrin-mediated energy-dependent manner. HA-Ag-PTX exhibits an excellent pH response release of PTX under the acidic condition, which is beneficial to enhance the distribution of PTX in the tumor microenvironment. HA-Ag-PTX effectively suppresses the migration and proliferation of LNCaP cells probably by arresting the cellular cycle at GO/G1 phase and enhancing the production of the reactive oxygen species. It is worth mentioning that HA-Ag-PTX exhibits greater anticancer activity in comparison with free PTX in the LNCaP cell model, indicating that HA-Ag NPs can effectively enhance the anticancer efficacy of PTX. As a whole, these findings suggest that HA-Ag-PTX has promising potential for PC therapy.