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[Cellular uptake behavior of antisense oligodeoxynucleotides polymethacrylate submicroparticles]
Wen-Xi Wang1, Wen-Quan Liang, Bi-Wei Song
1College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China.
Yao Xue Xue Bao = Acta Pharmaceutica Sinica
|January 18, 2006
Summary
Antisense oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) significantly enhance oligonucleotide uptake in MGC cells. This delivery method facilitates endocytosis and lysosomal escape for improved therapeutic potential.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Biology
Context:
- Antisense oligodeoxynucleotides (AS-ODNs) are crucial for gene silencing therapies.
- Efficient cellular delivery of AS-ODNs remains a significant challenge.
- Polymethacrylate submicroparticles (SMPs) offer a potential solution for enhanced drug delivery.
Purpose:
- To investigate the cellular uptake and intracellular distribution of AS-ODN-SMPs in MGC cell lines.
- To elucidate the mechanism of AS-ODN-SMP mediated cellular entry.
- To assess the impact of AS-ODN-SMPs on AS-ODN bioavailability within cells.
Summary:
- AS-ODN-SMPs demonstrated a remarkable 683-fold increase in cellular uptake compared to free AS-ODNs.
- Uptake was temperature-dependent, significantly higher at 37°C than 4°C, indicating an active process.
- Intracellular fluorescence intensity was comparable with or without chloroquine, suggesting lysosomal escape.
Impact:
- AS-ODN-SMPs represent a promising nanocarrier system for efficient oligonucleotide delivery.
- The endocytosis and lysosomal escape mechanism highlights the therapeutic potential of this formulation.
- This study provides a foundation for developing advanced oligonucleotide-based therapeutics.