Expanding Anti‐Stokes Shifting in Triplet–Triplet Annihilation Upconversion for In Vivo Anticancer Prodrug Activation

• Published in: Angewandte Chemie International Edition Vol. 56; no. 46; pp. 14400 - 14404
• Main Authors: Huang, Ling, Zhao, Yang, Zhang, He, Huang, Kai, Yang, Jinyi, Han, Gang
• Format: Journal Article
• Language: English
• Published: Germany 13.11.2017
• Subjects: Activation, Metabolic; Animals; anti-Stokes shifts; anticancer; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; BODIPY; Cell Line, Tumor; Chlorambucil - administration & dosage; Chlorambucil - chemistry; Chlorambucil - pharmacokinetics; Drug Delivery Systems; Heterografts; Humans; Light; Mice; Microscopy, Electron, Transmission; Nanoparticles; Polymers - chemistry; prodrug activation; Prodrugs - administration & dosage; Prodrugs - chemistry; Prodrugs - pharmacokinetics; Spectrometry, Fluorescence; triplet–triplet annihilation upconversion; anti-Stokes shifts; triplet-triplet annihilation upconversion; BODIPY; prodrug activation; anticancer
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201704430

A strategy to expand anti‐Stokes shifting from the far‐red to deep‐blue region in metal‐free triplet–triplet annihilation upconversion (TTA‐UC) is presented. The method is demonstrated by in vivo titration of the photorelease of an anticancer prodrug. This new TTA system has robust brightness and the longest anti‐Stokes shift of any reported TTA system. TTA core–shell‐structured prodrug delivery capsules that benefit from these properties were developed; they can operate with low‐power density far‐red light‐emitting diode light. These capsules contain mesoporous silica nanoparticles preloaded with TTA molecules as the core, and amphiphilic polymers encapsulating anticancer prodrug molecules as the shell. When stimulated by far‐red light, the intense TTA upconversion blue emission in the system activates the anticancer prodrug molecules and shows effective tumor growth inhibition in vivo. This work paves the way to new organic TTA upconversion techniques that are applicable to in vivo photocontrollable drug release and other biophotonic applications. Seeing red: Triplet–triplet annihilation upconversion (TTA‐UC) has robust brightness and the record longest anti‐Stokes shift from far‐red to deep‐blue light. TTA core–shell‐structured nanocapsules photorelease coumarin–chlorambucil (Cou‐C) prodrug upon irradiation with low‐power density far‐red light‐emitting diode (LED) light, to achieve potent tumor growth inhibition in vivo.