An enzyme-responsive conjugate improves the delivery of a PI3K inhibitor to prostate cancer

The enzyme-responsive peptide drug conjugate specifically delivers the drug to prostate cancer cells. The PSA substrate is cleaved in the tumor interstitial space to release the dipeptide-linked TGX-D1, which enters the cells via overexpressed dipeptide transporters in prostate cancer cells. TGX-D1 is finally released from the dipeptide after cleavage of the ester linker inside the cells to exert its pharmacological effect. The intact peptide-drug conjugate may also enter the cells directly via endocytosis, and the ester bond can be cleaved inside the cells to release the active drug.185