Heavy‐Atom‐Modulated Supramolecular Assembly Increases Antitumor Potency against Malignant Breast Tumors via Tunable Cooperativity

Abstract

Triple-negative breast cancer (TNBC) remains with highest incidence and mortality rates among females, and a critical bottleneck lies in rationally establishing potent therapeutics against TNBC. Here, the self-assembled micellar nanoarchitecture of heavy-atom-modulated supramolecules with efficient cytoplasmic translocation and tunable photoconversion is shown, for potent suppression against primary, metastatic, and recurrent TNBC. Multi-iodinated boron dipyrromethene micelles yield tunable photoconversion into singlet oxygen and a thermal effect, together with deep penetration and subsequent cytoplasmic translocation at the tumor. Tetra-iodinated boron dipyrromethene micelles (4-IBMs) particularly show a distinctly enhanced cooperativity of antitumor efficiency through considerable expressions of apoptotic proteins, potently suppressing subcutaneous, and orthotopic TNBC models, together with reduced oxygen dependence. Furthermore, 4-IBMs yield preferable anti-metastatic and anti-recurrent efficacies through the inhibition of metastasis-relevant proteins, distinct immunogenic cell death, and re-education of M2 macrophages into tumoricidal M1 phenotype as compared to chemotherapy and surgical resection. These results offer insights into the cooperativity of supramolecular nanoarchitectures for potent phototherapy against TNBC.