Volume 45 Issue 8, August 2024

Cover Credit: Reduction-activatable PROTAC prodrug nanoparticles for tumor-targeted protein degradation and anticancer therapy. The reduction-activatable PROTAC prodrug nanoparticles (NPs) were engineered by self-assembly of the PROTAC-conjugated amphiphilic diblock copolymer and further functionalized with a CRGDK ligand. The resulting PROTAC prodrug NPs can specifically target tumor cells and be efficiently internalized by recognizing neuropilin-1 (NRP-1), which is overexpressed on the surface of tumor cells. Remarkably, the PROTAC prodrug NPs efficiently degraded the protein targets BRD4 and CDK9 for inhibiting tumor growth in an mouse model of MDA-MB-231 triple-negative breast cancer. More importantly, the PROTAC prodrug NP can serve as a platform for co-delivering chemotherapeutic agents (e.g., doxorubicin, DOX) to perform combinatory cancer therapy. (Doi: 10.1038/s41401-024-01266-z). See the article in pages 1740–1751.