The development of novel ladder‐type conjugated molecules is crucial for advancing supramolecular chemistry and material science. In this study, we report a straightforward synthesis of new alternating donor‐acceptor (D‐A) ladder‐type heteroarene, FCDTDPP, and demonstrate its application as photothermal agent for imaging and cancer therapy. FCDTDPP is constructed by vinylene bridge between cyclopentadithiophene (D) and diketopyrrolopyrrole (A) through intramolecular Friedel‐Crafts type reaction. FCDTDPP exhibits unique combination of good molecular planarity, efficient intra/inter‐molecular mixed D‐A interactions, and local aromaticity. These features collectively contribute to its broad and intense absorptions with narrow bandgap in red band of the spectra, coupled with multiple vibrational absorption feature, thereby enhancing non‐radiative decay process and resulting in efficient photothermal conversion property. FCDTDPP and its nanoparticles (NPs) exhibit superior photothermal conversion performance and stability under 660 nm laser irradiation. Moreover, in vitro studies reveal that FCDTDPP NPs possess excellent biocompatibility, low cytotoxicity, and robust photothermal therapeutic efficacy, a finding further corroborated by preliminary in vivo experiments in tumor‐bearing mice. This work charts a novel course for the molecular engineering of organic photothermal conversion systems, propelling relevant research forward.
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