Small molecule-mediated photothermal therapy induces apoptosis in cancer cells

Abstract

Cancer remains as one of the most life-threatening diseases in the whole world. Most of the therapeutic strategies to eradicate cancer are highly invasive leading to severe injury and trauma to the patients. In recent times, phototherapy emerged as one of the non-invasive therapeutic strategies for cancer treatment. However, development of novel small molecule photothermal agents remained a major challenge. To address this, herein, we have designed and synthesized a small molecule library having aromatic substituted-3-methoxy-pyrrole and 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene) malononitrile in a concise synthetic strategy. One of the library members (7H), self-assembled into spherical-like nanoparticles having <100 nm size in water and was found to exhibit remarkable increase in temperature under 740 nm NIR light. Interestingly, compound 7H homed into the lysosomal compartments and the lipid droplets (LDs) in the HCT-116 colon cancer cells within 3h and induced photothermal effect (PTT) followed by generation of reactive oxygen species (ROS) while irradiating under 740 nm NIR light for 10 min. Moreover, 7H triggered programmed cell death (apoptosis) to induce remarkable HCT-116 cell killing. This small molecule-mediated photothermal effect showed potential to be an interesting tool for the next-generation non-invasive cancer phototherapy.