Enhancing doxorubicin sensitivity in osteosarcoma via iRGD-modified biomimetic nanoparticles targeting MCAM m6A
Dongjian Song1,2, Qiuliang Liu3, Da Zhang3
1Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China. songdjhenan@foxmail.com.
Journal of Translational Medicine
|July 17, 2025
Summary
Targeted nanoparticles delivering METTL3 inhibitors overcome doxorubicin resistance in osteosarcoma by regulating MCAM. This approach shows promise for treating resistant cancers.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Doxorubicin (Dox) resistance is a major obstacle in osteosarcoma (OS) treatment.
- Targeted delivery systems are needed to enhance therapeutic efficacy in resistant OS.
Purpose of the Study:
- To investigate iRGD-modified biomimetic nanoparticles (NPs) for targeted delivery of METTL3 inhibitors.
- To address Dox resistance in OS by regulating MCAM m6A modification.
Main Methods:
- Fabrication of OS cell membrane-coated lipid NPs with iRGD peptide modification.
- Loading NPs with METTL3 inhibitor STM2457 and evaluating stability, encapsulation, and cellular uptake.
- Assessing in vitro functional effects and in vivo therapeutic efficacy in a mouse xenograft model.
Main Results:
- iRGD-modified NPs demonstrated high stability, drug encapsulation, and cellular uptake.
- METTL3 inhibition decreased proliferation and invasion of Dox-resistant OS cells by reducing MCAM m6A.
- Combination therapy significantly inhibited tumor growth and lung metastasis in vivo.
Conclusions:
- iRGD-modified biomimetic NPs effectively overcome Dox resistance in OS.
- Targeting the METTL3-MCAM axis offers a potential strategy for resistant cancers.
- This approach holds promise for clinical translation in treating resistant osteosarcoma.
