Aggregation‐Enhanced Asymmetric Heptamethine Cyanine Nanoplatform for Imaging‐Guided Synergistic Phototherapy and Ferroptosis
Mengyuan Cui, Wenqing Li, Yanli Chen, Huijia Liu, Li Liu, Min Ji, Peng Wang
Abstract
ABSTRACT Current phototherapeutic agents based on heptamethine cyanine dyes often rely on symmetric structures, limiting their photodynamic therapy (PDT) efficiency. Herein, we report a novel asymmetric heptamethine cyanine dye (Cyp‐TPE) that features a twisted tetraphenylethylene moiety. This design facilitates the formation of stable aggregate nanoparticles (NPs) with a cross‐arranged structure, as revealed by molecular dynamics simulations. This specific aggregation mode promotes exciton delocalization and dramatically enhances spin‐orbit coupling, leading to an unprecedented ROS quantum yield of 154.54%. Under 808 nm laser irradiation, the Cyp‐TPE NPs demonstrate potent synergistic photodynamic and photothermal activity, concurrently triggering ferroptosis and lysosomal dysfunction, thereby achieving multimodal death of cancer cells. Furthermore, the excellent NIR absorption and photothermal conversion of these aggregates enable precise photothermal imaging (PTI) and photoacoustic imaging (PAI). This work highlights the potential of asymmetric molecular design to overcome the limitations of conventional photosensitizers, offering a robust nanoplatform for imaging‐guided cancer therapy.