A dual-locked cyclopeptide-siRNA conjugate for tumor-specific gene silencing.

ABSTRACT: Strategies allowing tumor-selective siRNA delivery while minimizing off-tumor gene silencing effects are highly demanded to advance cancer gene therapy, which however still remain challenging. We herein report a dual-locking bioconjugation approach to address this challenge. A dual-locked cyclopeptide-siRNA conjugate (DPRC) was designed to simultaneously endow siRNA with tumor-targeting properties and tumor-biomarker/visible-light dually controllable action. The DPRC consisted of a programmed death-ligand 1 (PD-L1)-targeting cyclopeptide as a tumor-homing ligand and B-cell lymphoma-2 (Bcl-2)-targeting siRNA as a payload. They were conjugated via a tandem-responsive cleavable linker containing a photocleavable coumarin moiety quenched by naphthylamide through a disulfide linkage. Owi

SUBMITTER: Li C 

PROVIDER: S-EPMC11612639 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature