Atomic‐iodine‐substituted polydiacetylene nanospheres with boosted intersystem crossing and nonradiative transition through complete radiative transition blockade for ultraeffective phototherapy

The energy dissipation pathways of a photosensitizer for phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), compete directly with that of its fluorescence (FL) emission. Enriching heavy atoms on the π‐conjugated systems and aggregation‐caused quenching are two effective methods to turn off the FL emission of photosensitizers, which is expected to boost the intersystem crossing (for PDT) and nonradiative transition (for PTT) of photosensitizers for maximized phototherapeutic efficacy. Following this approach, an all‐iodine‐substituted polydiacetylene aggregate poly(diiododiacetylene) (PIDA) has been developed, which shows a superior near infrared absorption (ε808nm = 26.1 g−1 cm−1 L) with completely blocked FL, as well as high efficiency of reactive oxygen species generation (nearly 45 folds of indocyanine green) and photothermal conversion (33.4%). To make the insoluble fibrillar PIDA aggregates favorable for systemic administration, they are converted into nanospheres through a pre‐polymerization morphology transformation strategy. The in vivo study on a 4T1 tumor‐bearing mouse model demonstrates that PIDA nanospheres can almost eliminate the tumor entirely in 16 days and prolong the survival time of mice to over 60 days, validating their effective phototherapeutic response through the strategy of inhibiting FL for boosted intersystem crossing and nonradiative transition. An atomic‐iodine‐substituted polydiacetylene aggregate poly(diiododiacetylene) (PIDA) was developed to completely block fluorescence emission via heavy atom effects as well as indefinitely extended π‐conjugation. The special structure gives it ultraeffective phototherapy effects under NIR light irradiation. By a newly preparation method, the morphology of PIDA dispersion transformed from fibers to nanospheres, which was suitable for i.v. systematically treatment.