Author: Material Treasure Box
Radiation is one of the main options for clinical cancer, however, the tumor's tolerance to radiation** and *** seriously affect the efficacy. Previous radiation** regimens had severe and tumor tolerance issues.
In this regard,School of Chemistry and Molecular Engineering, East China Normal UniversityXu ZhiaiProfessorsZhang WenProfessor, State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciencesto the NavyProfessorsTeamA PROTAC nanosensitizer for cancer radiation** was constructed. The study, titled "Protacprodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer", was published in Advmater.on.
The RPB7H nanoparticles reported in this paper have obvious advantages over traditional radiosensitizers. First, CRGDK ligand-modified RPB7H can bind to the NRP-1 receptor overexpressed on the surface of tumor cells, ensuring tumor-specific radiosensitization. Second, the physical sensitizer HFO nanoparticles are able to deposit X-rays in tumor tissues, leading to RT-induced DNA damage and oxidative stress. In addition, R-elevated Ho specifically activates the HO-responsive Protac prodrug BPA771 to degrade BRD4, thereby inhibiting R-induced RAD51AP1 upregulation, blocking X-ray-induced DDR via the BRD4-RAD51AP1 axis, and ultimately attenuating acquired radioimmunity. Therefore, this 2-in-1 RPB7H nanoparticle synergistically enhances the RT efficacy of HNSCC by simultaneously promoting DNA damage and hindering DDR.
Schematic diagram 1a) The response mechanism of RT triggers the activation of the BRD4-PROTAC prodrug. b) HFO nanoparticles and ProTAC prodrug double-loaded RPB7H nanoparticles.
Figure 1RT-induced activation of the BRD4-RAD51AP1 pathway and BRD4-PROTAC prodrug sensitization of HNSCC tumor cells to RT through BRD4 degradation.
Figure 2Tumor-targeted PROTAC prodrug nanoparticles in vitro to RT-sensitized HNSCC tumor cells.
Figure 3RPB7H nanoparticles sensitize tumor cells to ionic radiation by inhibiting the BRD4-RAD51AP1 pathway in vitro.
Figure 4RPB7H nanoparticles accumulate specifically at the tumor site in vivo and penetrate deep into the tumor.
Figure 5Accumulation of RPB7H nanoparticles in vivo sensitizes HN30 tumors to RT.
Notably, the ingredients used in the authors' study, PEG-B-PLGA and HFO, were both FDA-approved, which raises hope for their clinical application. To date, this is the first study utilizing PROTAC technology for RT sensitization, providing a groundbreaking strategy for RT enhancement of HNSCC.
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