Dynamic Covalent Prodrug Nanocomplex for Ultrasound-Triggered Oxidative Stress Amplification and Synergistic Sonochemotherapy.

Authors

Hancheng Jiang, Jianxin Rong, Yu Guo, Yingjian Cui, Xiaoya Wu, Jiahui Cong, Junhan Zhang, Weiqi Wang, Zhigang Xie, Xiuli Hu

Published in

Small (Weinheim an der Bergstrasse, Germany). Pages e76195. Oct 11, 2026. Epub Oct 11, 2026.

Abstract

Essential micronutrient Vitamin B₂ (VB₂) is a bioactive compound with sonodynamic activity; however, it suffers from hydrophilic limitations. Herein, a dynamic prodrug nanocomplex (PTX-PBA/VB₂) was constructed via phenylboronic acid-diol interaction between VB₂ and phenylboronic acid-functionalized paclitaxel prodrug (PTX-PBA). This reversible boronate ester linkage ensures colloidal stability while enabling external stimuli- or tumor microenvironment-triggered drug release. Under ultrasound irradiation, the nanocomplex generates singlet oxygen (¹O₂) and hydroxyl radical, inducing prodrug cleavage, on-demand paclitaxel release, glutathione depletion, and glutathione peroxidase 4 downregulation, leading to amplified oxidative stress and immunogenic cell death. Prolonged intratumoral retention (>7 days) was realized by loading PTX-PBA/VB₂ nanocomplex into an injectable poly(amino acid) hydrogel. In vivo study presented remarkable tumor suppression in 4T1-bearing mice, attributed to enhanced intratumoral reactive oxygen species levels and lipid peroxidation accompanied by robust immune activation. This work establishes a promising dynamic covalent prodrug strategy for precise sonoimmunotherapy.

PMID:
42859969
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.

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