Sahu, AsimaAsimaSahuIngle, JaypalsingJaypalsingInglePanigrahi, RehaRehaPanigrahiBasu, SudiptaSudiptaBasu2025-08-312025-08-312025-07-1810.1002/cmdc.2025001512-s2.0-105006449045https://d8.irins.org/handle/IITG2025/2805840346638Cancer 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 has emerged as one of the noninvasive therapeutic strategies for cancer treatment. However, development of novel small-molecule photothermal agents remains a major challenge. To address this, herein, a small molecule library having aromatic substituted-3-methoxy-pyrrole and 2-(3-cyano-4,5,5-trimethylfuran-2(5 H)-ylidene) malononitrile in a concise synthetic strategy is designed and synthesized. One of the library members (7H) self-assembles into spherical-like nanoparticles having <100 nm size in water and is found to exhibit remarkable increase in temperature under 740 nm near-infrared (NIR) light. Interestingly, compound 7H homes into the lysosomal compartments and the lipid droplets in the HCT-116 colon cancer cells within 3 h and induces photothermal effect followed by generation of reactive oxygen species while irradiating under 740 nm NIR light for 10 min. Moreover, 7H triggers programmed cell death (apoptosis) to induce remarkable HCT-116 cell killing. This small molecule-mediated photothermal effect shows potential to be an interesting tool for the next-generation noninvasive cancer phototherapy.falselipid droplets | lysosomes | near-infrared light irradiation | photothermal effects | small molecule libraryArticlehttps://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cmdc.2025001511860718718 July 20250e202500151arJournal1WOS:001494691600001