Synergistic Inter‐ and Intramolecular Aggregation of Dimeric Cyanine Dyes Affords Highly Efficient In Vivo Self‐Delivery and Photothermal Therapy

Abstract Advancing photothermal therapy hinges on developing PTAs with robust in vivo delivery and therapeutic efficacy. However, effective molecular design approaches for high‐performance PTAs remain lacking. Herein a strategic design of dimeric heptamethine cyanine (Cy7) molecules is presented, covalently linked via ortho/meta/para‐phenyldithiol. These designs facilitate spontaneous nanoparticle assembly in water, attributed to efficient intermolecular aggregation, enhancing in vivo delivery. Additionally, aggregation between intramolecular Cy7 units promotes superior photothermal conversion efficiency (PCE) up to 74.1% for meta‐dimer. Remarkably, the para‐dimer variant not only achieves a high PCE of 61.1% but also exhibits the most effective pharmacokinetic profile, leading to unparalleled anticancer efficacy in vivo. This dual aggregation strategy, leveraging both inter‐ and intramolecular dynamics, equips dimeric Cy7 with superior self‐delivery and photothermal efficacy, offering a promising approach for the next generation of photothermal therapeutics.