Heat-sensitive poly-acrylamide nanoparticle for cancer treatment

Abstract

Several nanomedicine-based platforms, including polymeric micelles, dendrimers, and liposomes, have been developed and explored for targeted delivery of therapeutics in cancer. These nanoparticles are capable of delivering selectively antineoplastic agents to the tumor, reduce the untoward toxicity, and improve the therapeutic effect. In the present study, we propose new thermosensitive polyacrylamide-based nanoparticles as polymer-based drug carriers. Polyacrylamide has a controllable swelling temperature, which enables a rapid release of an encapsulated drug above certain temperatures. PAA-NP was synthesized then functionalized with folic acid to improve selective targeting. Then doxorubicin, an antineoplastic agent, was encapsulated inside of the polymeric core. Our data show that these nanoparticles have a sol-gel transition temperature of 41°C. We investigated the effects of the folic acid functionalized PAA nanoparticles on HeLa cells both in vitro and in vivo, and on zebrafish larvae xenografted with human pancreatic cancer cell line Mia Paca-2. Functionalized NPs were internalized in a short time by the cancer cells, mainly localizing in the lysosomes. In vitro and in vivo cytotoxicity studies indicated high viability of cells treated with functionalized nanoparticles encapsulating doxorubicin by signaling a minor release of doxorubicin at physiological temperatures. Conversely, at the temperature of 41 °C, they trigger apoptosis of the xenografted cells, resulting in a strong arrest of the increase of the tumor area. Our results suggest that the heat-activated DOX:PAA-NP-FA could be used to implement combined therapies for the local treatment of solid cancers.