Near-infrared light-triggered prodrug photolysis by one-step energy transfer

• Published in: Nature communications 2023-12, Vol.14 (1), p.8112-8112, Article 8112
• Main Authors: Long, Kaiqi, Lv, Wen, Wang, Zihan, Zhang, Yaming, Chen, Kang, Fan, Ni, Li, Feiyang, Zhang, Yichi, Wang, Weiping
• Format: Article
• Language: English
• Subjects: 119/118; 14/19; 140/125; 140/131; 140/58; 59; 631/67/1059/153; 639/638/309/152; 639/638/403/934; Aqueous environments; Boron; Cancer therapies; Drug delivery; Drug delivery systems; Drugs; Efficiency; Energy consumption; Energy transfer; Humanities and Social Sciences; I.R. radiation; Irradiance; Lesions; Ligands; multidisciplinary; Near infrared radiation; Photolysis; Phototoxicity; Prodrugs; Science; Science (multidisciplinary); Therapy; Upconversion
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43805-y

Prodrug photolysis enables spatiotemporal control of drug release at the desired lesions. For photoactivated therapy, near-infrared (NIR) light is preferable due to its deep tissue penetration and low phototoxicity. However, most of the photocleavable groups cannot be directly activated by NIR light. Here, we report a upconversion-like process via only one step of energy transfer for NIR light-triggered prodrug photolysis. We utilize a photosensitizer (PS) that can be activated via singlet-triplet (S-T) absorption and achieve photolysis of boron-dipyrromethene (BODIPY)-based prodrugs via triplet-triplet energy transfer. Using the strategy, NIR light can achieve green light-responsive photolysis with a single-photon process. A wide range of drugs and bioactive molecules are designed and demonstrated to be released under low-irradiance NIR light (100 mW/cm 2 , 5 min) with high yields (up to 87%). Moreover, a micellar nanosystem encapsulating both PS and prodrug is developed to demonstrate the practicality of our strategy in normoxia aqueous environment for cancer therapy. This study may advance the development of photocleavable prodrugs and photoresponsive drug delivery systems for photo-activated therapy. Prodrug photolysis enables spatiotemporal control of drug release at the desired lesions, but most of the photocleavable groups cannot be directly activated by near-infrared (NIR) light that features deep penetration and low phototoxicity. Here, the authors report an upconversion-like process via only one step of energy transfer for NIR light-triggered prodrug photolysis.