Cyanine Nanoassemblies for synergistic cancer therapy: From aggregate-state modulation to Phototheranostic integration

The unique photophysical properties of cyanine dyes—strong NIR absorption, large molar extinction coefficients, and flexible structural tunability—have positioned them as an important class of photosensitizers for photothermal therapy (PTT) and photodynamic therapy (PDT). However, free cyanine dyes suffer from intrinsic limitations, including poor stability, aggregation-caused quenching (ACQ), low ROS generation, and rapid clearance, which severely restrict their biomedical utility. Recent advances in molecular self-assembly now offer powerful strategies to overcome these obstacles. Through π–π stacking, hydrophobic interaction, electrostatic association, peptide/protein templating, or metal-ion coordination, cyanine dyes can be organized into highly ordered nanostructures—such as J-aggregates, H-aggregates, nanomicelles, and hybrid nanoassemblies—with precisely tunable morphology and optical behavior. These nanoassemblies restrict conformational freedom, stabilize the excited state, suppress ACQ, and markedly enhance ROS yield and photothermal conversion. In particular, J-aggregates enable red-shifted and sharpened absorption bands, improving tissue penetration and energy utilization for deep-tissue phototherapy. Beyond enhancing PDT/PTT performance, self-assembled cyanine nanostructures integrate naturally into multifunctional platforms capable of tumor targeting, tumor microenvironment (TME)-responsive activation, multimodal imaging, and combination therapy—such as PTT–PDT synergy, chemo-phototherapy, SDT, or immunotherapy. Despite these promising advances, challenges remain, including controlling assembly stability in vivo, achieving batch-to-batch reproducibility, and predicting biological fate in complex physiological environments. This review summarizes recent progress in cyanine-dye self-assembly, with emphasis on assembly mechanisms, aggregate-state engineering, structure–property relationships, and strategies for improving PDT/PTT efficacy and combination cancer therapy. We further discuss existing limitations and future opportunities for translating assembled cyanine nanotherapeutics into precision oncology. Together, these insights highlight the power of supramolecular engineering in transforming traditional cyanine dyes into robust, versatile, and clinically meaningful phototheranostic nanoplatforms.