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Targeting glucose uptake with siRNA-based nanomedicine for cancer therapy
Cong-Fei Xu1, Yang Liu2, Song Shen2
1Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, Anhui, China.
Abstract:
Targeting cancer metabolism is emerging as a successful strategy for cancer therapy. However, most of the marketed anti-metabolism drugs in cancer therapy do not distinguish normal cells from cancer cells, leading to severe side effects. In this study, we report an effective strategy for cancer therapy through targeting glucose transporter 3 (GLUT3) with siRNA-based nanomedicine to simultaneously inhibit the self-renewal of glioma stem cells and bulk glioma cells in a glucose restricted tumor micro-environment. We have demonstrated that cationic lipid-assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles can efficiently deliver siRNA into U87MG and U251 glioma stem cells and bulk glioma cells. Nanoparticles carrying specific siRNA targeting GLUT3 (NPsiGLUT3) were able to significantly reduce the expression of GLUT3 in glioma stem cells and bulk glioma cells, while GLUT3 knockdown results in obvious cell metabolism and proliferation inhibition, and further glioma stem cells percentage down-regulation. Moreover, systemic delivery of NPsiGLUT3, via intravenous injection, significantly inhibited tumor growth in a U87MG xenograft model, due to the reduced expression of GLUT3 and down-regulated stemness of glioma cells.
Insights
This study developed novel nanomedicine to target glucose transporter 3 (GLUT3) in glioma cells. This approach effectively inhibits cancer cell self-renewal and tumor growth, offering a more targeted cancer therapy.
Area of Science:
- Oncology
- Nanomedicine
- Cancer Metabolism
Background:
- Targeting cancer metabolism is a promising therapeutic strategy.
- Current anti-metabolism drugs lack specificity, causing severe side effects.
- Glioma stem cells contribute to tumor recurrence and treatment resistance.
Purpose of the Study:
- To develop a targeted therapy for glioma by inhibiting glucose transporter 3 (GLUT3).
- To assess the efficacy of siRNA-based nanomedicine in reducing glioma cell self-renewal and tumor growth.
- To investigate the impact of GLUT3 inhibition on glioma stem cell populations.
Main Methods:
- Cationic lipid-assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles were synthesized.
- Nanoparticles delivered siRNA targeting GLUT3 (NPsiGLUT3) into U87MG and U251 glioma cells.
- In vivo studies utilized a U87MG xenograft model with intravenous NPsiGLUT3 administration.
Main Results:
- NPsiGLUT3 efficiently reduced GLUT3 expression in glioma stem and bulk cells.
- GLUT3 knockdown significantly inhibited cell metabolism, proliferation, and reduced glioma stem cell percentage.
- Systemic NPsiGLUT3 delivery suppressed tumor growth in vivo.
Conclusions:
- siRNA-based nanomedicine targeting GLUT3 offers a specific strategy for glioma therapy.
- This approach effectively inhibits glioma stem cell self-renewal and bulk tumor growth.
- Targeting GLUT3 represents a viable therapeutic avenue for reducing glioma progression and recurrence.
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