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Published on: February 5, 2019
CaF2 nanoparticles deliver siRNA targeting STAT6 and PPAR- γ to depolarise tumour-associated macrophages
Hamed Al-Busaidi1,2, Won Fen Wong3, Lakshmi Selvaratnam1
1Jeffrey Cheah School of Medicine & Health Sciences, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia.
Abstract:
Breast cancer is a leading cause of death in women, partly due to challenges posed by constituents of the tumour-microenvironment, such as tumour-associated macrophages (TAMs). Polarisation of macrophages to a pro-tumour phenotype usually involves STAT6 and PPAR- pathways. In this study, CaF2 nanoparticles were developed and bound to siRNA to inhibit the expression of STAT6 and PPAR- in an in vitro model of TAMs. CaF2 nanoparticles were synthesised by precipitation reactions and characterised by spectrophotometry, dynamic light scattering, FTIR, electron microscopy and MTT assay. Their binding affinity to siRNA was confirmed, as was the cellular uptake by TAMs. CaF2-bound siRNAs targeting STAT6 and PPAR- were found to reduce the expression of M2 phenotype when assessed by PCR and microscopy. These findings open the possibility of using nanoparticle-bound siRNA to target genes associated with pro-tumour polarisation in macrophages, with further potential to repolarise them to a more inflammatory phenotype.
Insights
Calcium fluoride nanoparticles carrying siRNA effectively silenced STAT6 and PPAR-γ genes in tumor-associated macrophages (TAMs). This approach shows promise for targeting pro-tumorigenic pathways in breast cancer therapy.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Nanomedicine
Background:
- Breast cancer poses a significant mortality risk, with tumor-associated macrophages (TAMs) contributing to its progression.
- Pro-tumorigenic polarization of TAMs is often mediated by STAT6 and PPAR-γ signaling pathways.
- Targeting these pathways offers a potential therapeutic strategy for breast cancer.
Purpose of the Study:
- To develop calcium fluoride (CaF2) nanoparticles functionalized with siRNA to inhibit STAT6 and PPAR-γ expression in TAMs.
- To evaluate the efficacy of CaF2-nanoparticle-siRNA complexes in an in vitro TAM model.
- To explore the potential of this nanomedicine approach for modulating the tumor microenvironment in breast cancer.
Main Methods:
- CaF2 nanoparticles were synthesized and characterized using spectrophotometry, dynamic light scattering, FTIR, electron microscopy, and MTT assay.
- Binding affinity of CaF2 nanoparticles to siRNA was confirmed, along with their cellular uptake by TAMs.
- Quantitative PCR and microscopy were employed to assess gene expression and M2 phenotype reduction.
Main Results:
- CaF2 nanoparticles demonstrated successful binding to siRNA and uptake by TAMs.
- The CaF2-nanoparticle-siRNA complexes significantly reduced the expression of STAT6 and PPAR-γ.
- A notable decrease in the M2 pro-tumor phenotype of TAMs was observed.
Conclusions:
- CaF2 nanoparticles serve as an effective delivery vehicle for siRNA targeting STAT6 and PPAR-γ in TAMs.
- This strategy can inhibit pro-tumorigenic gene expression and reduce the M2 phenotype in TAMs.
- Nanoparticle-mediated siRNA delivery presents a promising avenue for breast cancer therapy by modulating the tumor microenvironment.
