131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy

For the first time, this study proves that131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). Both in vitro and in vivo experiments prove that co-administration of131I and azoPROTAC can not only effectively down-regulate the BRD4 protein, but also exhibit excellent tumor inhibition with BRD4 degradation enhanced radiotherapeutic and immunological effect. AbstractPhotopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50  µCi mL−1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405  nm, 60 mW cm−2). What's more, the degradation of BRD4 can further benefit the131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of131I (300 µCi) and azoPROTC (25 mg kg−1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research