High-performance photosensitizers are highly desired for achieving selective tumor photoablation in the field of precise cancer therapy. However, photosensitizers frequently suffer from limited tumor suppression or unavoidable tumor regrowth due to the presence of residual tumor cells surviving in phototherapy. A major challenge still remains in exploring an efficient approach to promote dramatic photoconversions of photosensitizers for maximizing the anticancer efficiency. Here, a rational design of boron dipyrromethene (BDP)-based conjugated photosensitizers (CPs) that can induce dually cooperative phototherapy upon light exposure is demonstrated. The conjugated coupling of BDP monomers into dimeric BDP (di-BDP) or trimeric BDP (tri-BDP) induces photoconversions from fluorescence to singlet-to-triplet or nonradiative transitions, together with distinctly redshifted absorption into the near-infrared region. In particular, tri-BDP within nanoparticles shows preferable conversions into both primary thermal effect and minor singlet oxygen upon near-infrared light exposure, dramatically achieving tumor photoablation without any regrowth through their cooperative anticancer efficiency caused by their dominant late apoptosis and moderate early apoptosis. This rational design of CPs can serve as a valuable paradigm for cooperative cancer phototherapy in precision medicine.

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.

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