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, to reduce the untoward toxicity and improve the therapeutic effect. In the present study, we propose new thermo-sensitive poly-acrylamide based nanoparticles (PAA-NP) as polymer-based drug carriers. Poly-acrylamide has a controllable swelling temperature, enabling a rapid release of the encapsulated drug at high temperatures, induced by irradiation of energy. The PAA-NP were synthesized and functionalized on the surface with folic acid (FA), to improve the selective targetability of the system. Moreover, the doxorubicin (DOX), as an antineoplastic agent, was encapsulated and protected inside the polymeric core. We investigated the effects of our DOX:PAA-NP-FA both in vitro, on HeLa cells and in vivo, on zebrafish larvae xenografted with human pancreatic cancer cell line Mia Paca-2. Our data showed that particles have a sol-gel transition temperature of about 41°C. They were easily internalized in a short time by cancer cells and mainly localized in the lysosomes. Moreover, in vitro and in vivo cytotoxicity studies reported a high viability of cells treated with DOX:PAA-NP-FA, indicating a negligible release of the doxorubicin at physiological temperature. 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.