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For example, nano-PROTACs composed of a photosensitizer (protoporphyrin IX, PpIX) and a Src homology 2 domain-containing phosphatase 2 (SHP2)-targeting PROTAC peptide (aPRO) connected by a caspase-3 cleavable linker, among them aPRO is activated after phototherapy due to the increased expression of caspase-3 in tumor cells, inducing the targeted degradation of SHP2 through the ubiquitin-proteasome system, and the persistent depletion of SHP2 blocks the immunosuppressive checkpoint signaling pathways CD47/SIRPα and PD-1/PD-L1 thereby reactivating anti-tumor macrophages and T cells (239)
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