Novel Engineered Microgels with Amphipathic Network Structures for Simultaneous Tumor and Inflammation Depression.

Novel engineered microgels with amphipathic network structures were designed and synthesized by copolymerizing N-isopropylacrylamide, 1-vinylimidazole, and 2-(cinnamoyloxy)ethyl methacrylate in the presence of 1,6-dibromohexane. The engineered microgels possess hydrophilic quaternization cross-linking structures and hydrophobic cross-linking inner nanodomains, which are suitable for loading and simultaneous release of hydrophilic nonsteroidal anti-inflammatory drug diclofenac sodium (DS) and hydrophobic antic cancer drug doxorubicin (DOX), respectively. The engineered microgels exhibited excellent stability, low cytotoxicity, and long blood circulation time and could be uptaken into the cytoplasm of cells, metabolized, and excreted from the living body by the kidney and the liver. In vivo experiments showed that with injection of DS and DOX dual-drug-loaded microgels, simultaneous antitumor treatment and inflammation depression were achieved along with high antitumor efficacy and low drug-related toxicity. Such microgels with amphipathic network structures have promising applications for combination therapy.