Orthogonally targeted tumor radiosensitization using cell penetrating peptide-ATM inhibitor conjugates to stimulate anti-tumor immune responses.

ABSTRACT: Tumor resistance to radiotherapy continues to be a significant problem in improving cancer patient outcomes. To overcome radioresistance, drugs that sensitize cancer cells to ionizing radiation have been tested. In theory, radiosensitizers should increase irradiated tumor kill and improve patient outcomes. In practice, the clinical utility of such drugs is curtailed by radiosensitization of peri-tumoral normal tissues causing toxicities. To address these issues, we developed an activatable cell penetrating peptide-drug conjugate to deliver a small molecule radiosensitizer with spatial precision to tumors. The activatable cell penetrating peptide (ACPP) scaffold cloaks a cell penetrating peptide-drug conjugate until it is unmasked within tumors through matrix metalloproteinase cleavage. Usi

SUBMITTER: Dhawan K 

PROVIDER: S-EPMC12871284 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature