空位缺陷诱导电子归巢效应断裂磷酸二酯键用于RNA清除驱动的癌症治疗

Abstract

Genome-wide hypertranscription is a hallmark of malignant progression. However, the development of precise and controlled RNA degradation within biological systems continues to pose significant challenges. Current base-pairing or RNase-based therapeutics rely on sequence recognition and inherent instability within the tumor microenvironment significantly diminishes therapeutic efficacy. Here, we establish a vacancy defect-induced electron homing strategy to achieve enzyme-free RNA degradation. Introducing 5% sulfur vacancies into Bi 2 S 3 disrupts the Bi-S coordination and induces lattice distortion, which drives electron accumulation at the bismuth center and enhances their adsorption with double-bonded oxygen in phosphodiester bonds. This vacancy-driven electron homing lowers the reaction barrier from 2.01 to 0.95 eV by enhancing Bi-O coordination, which polarizes the nearby P-O bond and facilitates nucleophilic attack at the phosphorus center. Valence electron redistribution efficiently breaks phosphodiester bonds to degrade RNA and induces tumor cell apoptosis. This mechanism significantly inhibits tumor proliferation by regulating ERI3 expression in vitro and in vivo. Our work demonstrates a physics-based approach for direct bond activation and establishes vacancy engineering as a general principle for tuning electron states and modulating bond reactivity in biological systems.