Redox-sensitive PMMA-core-shell nanoparticles as drug carriers for anti-cancer therapeutics

Modern chemotherapy aims to provide highly effective treatment with minimized side effects. In light of this aim, nanoparticle drug carriers for chemotherapeutic agents are gaining considerable interest. They can significantly improve the pharmacological profile of traditional chemotherapeutic agents, while introducing tunability of their release and distribution within the body. In the present study we imparted biodegradability and redox-sensitive properties on a proven core-shell PMMA nanoparticle system through the implementation of a Bis(2-methacryloyl)oxyethyl disulfide crosslinker as a drop-in replacement for the methyl methacrylate from the original system. The original emulsion polymerization pathway was utilized without significant alterations, employing 2-(dimethyl-octyl) ammonium ethyl methacrylate bromide both as a charged copolymer and a surfactant. The synthesis yielded nanoparticles (NPs) of high colloidal stability and high positive surface charge with diameters ranging from 113(9,39) nm to 149(2,79) nm and ζ-potentials - from 71(1,34) to 55(1,93). TGA was demonstrated to be a useful technique for assessing the synthesis efficiency and for analysing the NP composition. The charged surface of the NPs allowed for the electrostatic loading of Tetrasulfonated Aluminum Phthalocyanine photosensitizer, which retained its ROS-generating activity upon loading. Notably, the unloaded NPs themselves generated significant amounts of ROS upon irradiation. Degradation studies revealed that the NPs successfully decompose when exposed to a reducing environment. The incorporation of MMA as a copolymer was proven to decrease the polydispersity and slow down the degradation of the NPs. It also reduced their ROS production considerably. Finally, we demonstrated that introducing hydrophobic cargo (Nile Red dye) during the synthesis did not disrupt the polymerization process and yielded dye-containing nanoparticles, closely resembling their unloaded analogues.