Dual acid-responsive micelle-forming anticancer polymers as new anticancer therapeutics

Cinnamaldehyde, a major active compound of cinnamon, is known to induce apoptotic cell death in numerous human cancer cells. Here, dual acid-responsive polymeric micelle-forming cinnamaldehyde prodrugs, poly[(3-phenylprop-2-ene-1,1- diyl)bis(oxy)bis(ethane-2,1-diyl)diacrylate]-co-4,4'(trimethylene dipiperidine)-co-poly(ethylene glycol), termed PCAE copolymers, are reported. PCAE is designed to incorporate cinnamaldehyde via acid-cleavable acetal linkages in its pH-sensitive hydrophobic backbone and self assemble to form stable micelles which can encapsulate camptothecin (CPT). PCAE self assembles to form micelles which release CPT and cinnamaldehyde in pH-dependent manners. PCAE micelles induce apoptotic cell death through the generation of intracellular reactive oxygen species (ROS) and exert synergistic anticancer effects with a payload of CPT in vitro and in vivo model of SW620 human colon tumor-bearing mice. It is anticipated that dual acid-sensitive micelle-forming PCAE with intrinsic anticancer activities has enormous potential as novel anticancer therapeutics. Cinnamaldehyde is a major component of cinnamon and is known to exert anticancer effects by generating reactive oxygen species. In this work, cinnamaldehyde is polymerized to generate polymers (PCAE) which self-assemble to form micelles. PCAE micelles exert synergistic anticancer effects with a payload of anticancer drugs and have great potential as novel anticancer therapeutics.