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Glyco Ionic Liquids as Novel Nanoparticle Coatings to Enhance Triple-Negative Breast Cancer Drug Delivery
Gaya S Dasanayake1, Christine M Hamadani1, Fikir Hailu1
1Department of Chemistry and Biochemistry, University of Mississippi, University, MS, 38677, USA.
Abstract:
Targeted drug delivery seeks to revolutionize disease treatment by enhancing therapeutic efficacy and specificity. However, developing and achieving precisely targeted delivery remains a significant challenge, particularly in cancers such as triple-negative breast cancer (TNBC), which lack traditional markers for targeted delivery. TNBC cells overexpress glucose transport proteins (GLUTs) on their surfaces, providing an opportunity for targeting. Herein, sugar-based ionic liquids (Glyco-ILs or GILs) are developed and used to modify poly (lactic-co-glycolic acid) (PLGA) nanocarriers (NPs), show enhanced affinity and selectivity towards TNBC cells and human and mouse erythrocytes. Inhibition assays, molecular docking simulations, and liquid chromatography-mass spectrometry (LCMS) analysis data show that the enhanced nanoparticle affinity for TNBC cells is likely due to a combination of specific binding interactions with GLUT transporters and endocytosis. The observed RBC affinity is evidenced to be driven by interactions with RBC membrane GLUTs along with their unique serum protein corona on the nanoparticle surface. In vivo, experiments in a healthy BALB/c mouse model show that Glyco-IL-NPs demonstrate longer retention time in the bloodstream and a significant reduction in liver accumulation relative to the control. These findings suggest that Glyco-IL-modified PLGA nanoparticles (GIL-NPs) hold a promising approach for selective drug delivery, particularly in cells that overexpress GLUTs.
Insights
Sugar-based ionic liquids modify nanocarriers for targeted drug delivery, showing promise for treating cancers like triple-negative breast cancer (TNBC) by targeting glucose transporters. These modified nanoparticles exhibit improved selectivity and reduced liver accumulation in vivo.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery Systems
Background:
- Targeted drug delivery aims to improve treatment efficacy and specificity.
- Triple-negative breast cancer (TNBC) lacks traditional markers, posing challenges for targeted therapies.
- TNBC cells overexpress glucose transport proteins (GLUTs), presenting a potential therapeutic target.
Purpose of the Study:
- To develop sugar-based ionic liquids (Glyco-ILs or GILs) to modify poly(lactic-co-glycolic acid) (PLGA) nanocarriers (NPs).
- To investigate the enhanced affinity and selectivity of GIL-modified NPs (GIL-NPs) towards TNBC cells.
- To evaluate the in vivo performance of GIL-NPs in a mouse model.
Main Methods:
- Synthesis and modification of PLGA nanocarriers with Glyco-ILs.
- Inhibition assays, molecular docking, and LCMS analysis to determine binding interactions.
- In vivo studies in BALB/c mice to assess pharmacokinetics and biodistribution.
Main Results:
- GIL-NPs demonstrated enhanced affinity and selectivity for TNBC cells and erythrocytes.
- Specific binding interactions with GLUT transporters and endocytosis contributed to TNBC cell targeting.
- In vivo studies showed longer bloodstream retention and reduced liver accumulation of GIL-NPs compared to controls.
Conclusions:
- Glyco-IL modification of PLGA nanoparticles offers a promising strategy for selective drug delivery.
- This approach is particularly effective for targeting cells overexpressing GLUTs, such as those found in TNBC.
- GIL-NPs represent a potential advancement in cancer therapy and drug delivery systems.
