NGR-Modified CAF-Derived exos Targeting Tumor Vasculature to Induce Ferroptosis and Overcome Chemoresistance in...

Area of Science:

• Oncology
• Biotechnology
• Molecular Biology

Background:

• Chemoresistance is a major obstacle in osteosarcoma (OS) treatment.
• Novel therapeutic strategies are needed to enhance chemotherapy efficacy in OS.

Purpose of the Study:

• To investigate the use of NGR-modified cancer-associated fibroblasts (CAFs)-derived exosomes (exos) for delivering circ_0004872 to reverse chemoresistance in OS.
• To explore the mechanism of autophagy-dependent ferroptosis induced by circ_0004872-encoded small peptides.

Main Methods:

• Single-cell transcriptome analysis and high-throughput sequencing to identify chemoresistance-associated circRNAs.
• In vitro and in vivo experiments to evaluate the efficacy of NGR-modified CAFs-derived exos delivering circ_0004872.
• Assessment of autophagy-dependent ferroptosis induction.

Main Results:

• Circ_0004872 was identified as a key circular RNA associated with chemoresistance in OS.
• The small peptide encoded by circ_0004872 effectively reversed chemoresistance by promoting autophagy-dependent ferroptosis.
• NGR-modified CAFs-derived exos efficiently delivered circ_0004872 to OS cells, enhancing targeted therapy.

Conclusions:

• NGR-modified CAFs-derived exos represent a promising drug delivery system for OS.
• Targeting circ_0004872 to induce autophagy-dependent ferroptosis is a viable strategy to overcome OS chemoresistance.
• This approach holds potential for improving clinical outcomes in osteosarcoma patients.