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This research aims to develop a novel nanoplatform that combines ferroptosis and sonodynamic therapy for cancer treatment.

May 10, 2026Open Access

A ferroptosis-based intelligent nanoplatform with chemo-sonodynamic therapy carrying oxygen for improving tumor suppression and antitumor immunity

WWWeilin WangMinistry of Education QHQiaoying HuMinistry of Education CWChunyan WuMinistry of Education

Key Points

This research aims to develop a novel nanoplatform that combines ferroptosis and sonodynamic therapy for cancer treatment.
Fabrication of a nanoplatform (DTX-CS/ART/PFCA@RGD) using cyclic peptides and chondroitin sulfate for targeted delivery.
Investigation of nanoparticle effects on A549 cell apoptosis and the immune response in tumor-bearing mice.
Analysis of tumor hypoxia and immune modulation via HIF-1α and T cell dynamics.
Nanoparticles induced significant apoptosis in A549 cells, improving cancer cell death rates.
The treatment downregulated HIF-1α and alleviated hypoxia in tumors, enhancing sonodynamic therapy effectiveness.
The approach stimulated immunogenic cell death, increasing T cell and dendritic cell numbers in treated mice.

Abstract

Ferroptosis and sonodynamic therapy (SDT) have both been recognized as powerful weapons in cancer treatment, especially in non-small-cell lung carcinoma (NSCLC) recently. However, the lack of effective sono-sensitizer and ferroptosis regulator limited their usage. In order to overcome the limitation, a novel nanoplatform of DTX-CS/ART/PFCA@RGD (cRCAPD) was fabricated based on SDT and ferroptosis. Nanoparticles, under the action of c(RGDfk) cyclic peptides and their skeleton chondroitin sulfate (CS), could specifically target αvβ3 and CD44 receptors, respectively, thereby targeting tumor sites. Meanwhile, the peroxy-bridge structure of ART disrupted the intracellular iron homeostasis while generating highly toxic reactive oxygen species (ROS) under the SDT. Docetaxel (DTX) in nanoparticles led to the excellent apoptosis of A549 cells. Oxygen carried by PFCA alleviated the tumor hypoxic microenvironment, downregulated HIF-1α, and provided substrates for SDT. Further, the nanoparticles showed a strong immunogenic cell death (ICD) effect, modulating the number of T cells and dendritic cells in tumor-bearing mice. In summary, the proposed therapeutic strategy based on SDT and ferroptosis holds promising potential for synergistic treatment of lung cancer in future clinical applications.

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