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Ion interference induced by Ca-Mn nanoplatform enhances ferroptosis and promotes immune response for osteosarcoma
Minyi Zhang1, Qi Wang2, Chen Li1
1School of Chemical Science and Engineering, Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, PR China.
Introduction:
Ion interference therapy has emerged as a promising new treatment for Osteosarcoma (OS). However, its efficacy is significantly restricted by inadequate hydrogen peroxide (H2O2) under the complex tumor microenvironment (TME).
Objectives:
This study aimed to supply sufficient H2O2 to enhance tumor therapy efficacy and address the limitations associated with ion interference.
Methods:
A hollow manganese dioxide (HMnO2) nanoplatform loaded with calcium peroxide (CaO2) (denoted as HMnO2@CaO2) was evaluated for biosafety through hemolysis tests. The functionality of HMnO2@CaO2 was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and cytometric analysis.
Results:
Excessive Ca2+ accumulation induces endoplasmic reticulum (ER) stress, enhances oxidative stress, and causes mitochondrial damage. Notably, Mn2+ facilitates treatment monitoring through magnetic resonance imaging (MRI). Additionally, Mn2+-induced ferroptosis triggers an immune response that promotes the polarization of tumor-associated macrophages (TAMs), transforming the pro-tumoral M2 phenotype into the tumoricidal M1 phenotype, thereby enhancing the efficacy of immunotherapy.
Conclusion:
In conclusion, HMnO2@CaO2 nanoplatform enhances tumor therapy efficacy by overcoming ferroptosis limitations, inducing Ca2+ overload, and boosting anti-tumor immunity. This strategy offers a promising approach to ion interference in the clinical translation of nanomedicines. Furthermore, it marks a significant advancement in osteosarcoma (OS) treatment and underscores the transformative potential of nanotechnology in medicine.
Insights
This study developed a novel hollow manganese dioxide and calcium peroxide (HMnO2@CaO2) nanoplatform to boost ion interference therapy for Osteosarcoma. The nanoplatform effectively delivers hydrogen peroxide, enhances anti-tumor immunity, and enables treatment monitoring via MRI.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Ion interference therapy shows promise for Osteosarcoma (OS) treatment.
- Therapy efficacy is limited by insufficient hydrogen peroxide (H2O2) in the tumor microenvironment (TME).
Purpose of the Study:
- To enhance tumor therapy efficacy by supplying sufficient H2O2.
- To address limitations of ion interference therapy in Osteosarcoma.
Main Methods:
- Developed a hollow manganese dioxide (HMnO2) nanoplatform loaded with calcium peroxide (CaO2), denoted as HMnO2@CaO2.
- Evaluated biosafety via hemolysis tests and functionality using qRT-PCR and cytometric analysis.
Main Results:
- HMnO2@CaO2 induces Ca2+ overload, causing ER stress and mitochondrial damage.
- Mn2+ enables MRI-based treatment monitoring and promotes ferroptosis.
- Mn2+ enhances anti-tumor immunity by polarizing tumor-associated macrophages (TAMs) from M2 to M1 phenotype.
Conclusions:
- The HMnO2@CaO2 nanoplatform overcomes ferroptosis limitations, boosts anti-tumor immunity, and enhances OS therapy.
- This strategy shows promise for clinical translation of nanomedicines in Osteosarcoma treatment.
- Nanotechnology offers transformative potential in advancing cancer therapeutics.
