Fe-Polyphenol Self-Assembled Nanoplatform for Sonodynamic-Ferroptosis-Autophagy Inhibition Synergistic Tumor Therapy

作者：Chang Liu, Weiping Zhou, Shuang Song, Ying Li, Di He, Wenzhao Han, Cong Yu · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.5c09829 · 被引用次数：6 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Extracellular vesicles in disease

Effective tumor treatment still faces tough challenges. Sonodynamic therapy (SDT) has gained recognition as a viable substitute for photodynamic therapy, providing enhanced tissue penetration and reduced skin damage by generating reactive oxygen species (ROS) via ultrasound-triggered sonosensitizers. Nonetheless, the therapeutic efficacy of SDT is often hindered by the intrinsic apoptosis resistance of cancer cells. Additionally, apoptosis-resistant cancer cells often exhibit susceptibility to ferroptosis, making the development of an iron enrichment ferroptosis strategy crucial for the combined apoptosis–ferroptosis antitumor therapy. However, tumor cells often counteract apoptosis and ferroptosis by upregulating autophagy; thus, interrupting the autophagic degradation process is vital for the enhancement of the therapeutic outcome. Accordingly, we designed a metal–organic synergistic nanotherapeutic platform (Fe–Rh@IAA NPs) by incorporating iron, rhein, and indole-3-acetic acid (IAA) to target apoptosis, ferroptosis, and autophagy inhibition. Following systemic administration, Fe–Rh@IAA NPs were preferentially gathered at the tumor location, leveraging the enhanced permeability and retention effect. When exposed to ultrasonic irradiation, Fe–Rh@IAA NPs induced apoptosis via SDT, while the Fe ions induced ferroptosis through ROS production and glutathione depletion. At the tumor microenvironment with high concentrations of H 2 O 2, peroxidase-like activity of the nanoparticl...