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Iguratimod-encapsulating PLGA-NPs induce human multiple myeloma cell death via reactive oxygen species and
Faming Wang1, Muhammad Younis2, Yao Luo1
1Department of Biochemistry and Molecular Biology, Medical School of Southeast University, # 87 Dingjiaqiao Road, Nanjing 210009, China.
Abstract:
Human multiple myeloma (MM) is a currently incurable haematopoietic malignancies. Our research investigate the anti-tumour effect of iguratimod (IGU) encapsulated in poly(lactic-co-glycolic acid) PLGA nanoparticles (IGU-PLGA-NPs) on MM cells in vitro and in vivo. A significant inhibitory effect of IGU-PLGA-NPs on MM cancer cells and MM CSCs was demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Treatment with IGU-PLGA-NPs induced significant cell cycle arrest at G1 in MM cells and reduced tumour colony formation in MM CSCs. Mechanistically, IGU-PLGA-NPs increase apoptosis in MM cells by activating Caspase-dependent signalling pathway to increase the levels of bax, cytochrome c (cyt-c), caspase-9 and caspase-3 proteins. Moreover, IGU-PLGA-NPs effectively increase ROS production assayed using a DCFH-DA fluorescent probe in MM cells. The data indicate that IGU-PLGA-NPs induce a significant reduction in the tumour volume and a marked increase in the survival rate in a mouse model of multiple myeloma. Overall, our findings indicate that IGU-PLGA-NPs are a potential therapeutic strategy that may contribute to the therapy of MM and elimination of MM CSCs in future clinical trials.
Insights
Iguratimod encapsulated in PLGA nanoparticles shows significant anti-tumour effects against multiple myeloma (MM) cells and cancer stem cells (CSCs). This novel therapy reduces tumor volume and increases survival in MM mouse models.
Area of Science:
- Oncology
- Nanomedicine
- Pharmacology
Background:
- Multiple myeloma (MM) is an incurable blood cancer.
- Cancer stem cells (CSCs) contribute to MM progression and treatment resistance.
- Novel therapeutic strategies are needed for MM treatment.
Purpose of the Study:
- To investigate the anti-tumour effects of iguratimod (IGU) encapsulated in poly(lactic-co-glycolic acid) nanoparticles (IGU-PLGA-NPs).
- To evaluate the efficacy of IGU-PLGA-NPs against MM cells and MM CSCs in vitro and in vivo.
Main Methods:
- Cell Counting Kit-8 (CCK-8) assay to assess cell viability.
- Flow cytometry to analyze cell cycle arrest and apoptosis.
- DCFH-DA fluorescent probe to measure reactive oxygen species (ROS) production.
- In vivo studies using a mouse model of multiple myeloma.
Main Results:
- IGU-PLGA-NPs significantly inhibited MM cancer cells and MM CSCs proliferation.
- Treatment induced G1 cell cycle arrest in MM cells and reduced tumour colony formation in MM CSCs.
- IGU-PLGA-NPs promoted apoptosis via Caspase-dependent pathways and increased ROS production.
- In vivo, IGU-PLGA-NPs reduced tumour volume and increased survival rate in MM mice.
Conclusions:
- IGU-PLGA-NPs demonstrate potent anti-tumour activity against multiple myeloma.
- This nanoparticle formulation shows promise for eliminating MM CSCs.
- IGU-PLGA-NPs represent a potential therapeutic strategy for future clinical trials in MM treatment.
