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Surface functionalisation of PLGA nanoparticles for gene silencing
Morten Ø Andersen1, Agata Lichawska, Ayyoob Arpanaei
1Interdisciplinary Nanoscience Center (iNANO), Ny Munkegade 118, University of Aarhus, Aarhus C, Denmark.
Biomaterials
|May 4, 2010
Summary
This study enhances poly (lactide-co-glycolide) (PLGA) nanoparticles with cetylated polyethyleneimine (PEI) for improved siRNA delivery. The modified nanoparticles effectively deliver siRNA to cancer and immune cells, demonstrating significant gene silencing without toxicity.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Delivery
Background:
- Poly (lactide-co-glycolide) (PLGA) nanoparticles are widely used but require surface modification for efficient siRNA delivery.
- Polyethyleneimine (PEI) is a cationic polymer effective for nucleic acid complexation, but its surface presentation on nanoparticles can be limited.
Purpose of the Study:
- To develop a method for decorating PLGA nanoparticles with a cetylated derivative of PEI to enhance surface amine presentation.
- To evaluate the efficacy of these modified nanoparticles for siRNA delivery and gene silencing in cancer and immune cells.
Main Methods:
- Sub-micron PLGA nanoparticles were synthesized using an emulsion-diffusion method.
- Surface functionalization was achieved using a cetylated PEI derivative.
- X-ray photoelectron spectroscopy (XPS) was used to quantify surface amine density.
- Spectroscopy, fluorescent microscopy, and flow cytometry assessed nanoparticle binding and siRNA delivery.
- Gene silencing efficacy was evaluated by measuring BCL-w in U2OS cells and TNFalpha in J774.1 cells.
Main Results:
- The cetylated PEI modification resulted in a 2.6-fold increase in surface amine presentation compared to non-cetylated PEI (6.5% vs 2.5% surface nitrogen).
- Modified nanoparticles successfully bound to and mediated siRNA delivery into U2OS and J774.1 cell lines.
- 53% reduction in BCL-w oncogene expression was observed in U2OS cells with no observed toxicity.
- 64% silencing of TNFalpha was achieved in J774.1 cells using cetylated PEI modified nanoparticles.
Conclusions:
- Cetylated PEI modification is a rapid and effective strategy to enhance the surface functionalization of PLGA nanoparticles.
- These modified nanoparticles demonstrate potent siRNA delivery capabilities and gene silencing efficacy in relevant cell lines.
- The approach offers a promising platform for developing targeted nanotherapeutics with controllable biological properties.
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