Surface functionalisation of PLGA nanoparticles for gene silencing

Morten Andersen, Agata Lichawska, Ayyoob Arpanaei, Stig Møller Rask Jensen, Harpreet Kaur, David Oupicky, Flemming Besenbacher, Peter Kingshott, Jørgen Kjems, Kenneth A. Howard

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5% surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular toxicity. In addition, particles containing cetylated-PEI achieved 64% silencing of TNFα in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles.

Original languageEnglish (US)
Pages (from-to)5671-5677
Number of pages7
JournalBiomaterials
Volume31
Issue number21
DOIs
StatePublished - Jul 1 2010

Fingerprint

Polyethyleneimine
Gene Silencing
Nanoparticles
Genes
Derivatives
Small Interfering RNA
Cells
Benzyl Alcohol
Polyglactin 910
Cell Line
Photoelectron Spectroscopy
Flow cytometry
Macrophages
Osteosarcoma
Photoelectron spectroscopy
Emulsions
Tumor Suppressor Genes
Amines
Toxicity
Surface treatment

Keywords

  • Cetylated PEI
  • Drug delivery
  • PLGA
  • RNAi
  • SiRNA
  • Surface modification

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Andersen, M., Lichawska, A., Arpanaei, A., Rask Jensen, S. M., Kaur, H., Oupicky, D., ... Howard, K. A. (2010). Surface functionalisation of PLGA nanoparticles for gene silencing. Biomaterials, 31(21), 5671-5677. https://doi.org/10.1016/j.biomaterials.2010.03.069

Surface functionalisation of PLGA nanoparticles for gene silencing. / Andersen, Morten; Lichawska, Agata; Arpanaei, Ayyoob; Rask Jensen, Stig Møller; Kaur, Harpreet; Oupicky, David; Besenbacher, Flemming; Kingshott, Peter; Kjems, Jørgen; Howard, Kenneth A.

In: Biomaterials, Vol. 31, No. 21, 01.07.2010, p. 5671-5677.

Research output: Contribution to journalArticle

Andersen, M, Lichawska, A, Arpanaei, A, Rask Jensen, SM, Kaur, H, Oupicky, D, Besenbacher, F, Kingshott, P, Kjems, J & Howard, KA 2010, 'Surface functionalisation of PLGA nanoparticles for gene silencing', Biomaterials, vol. 31, no. 21, pp. 5671-5677. https://doi.org/10.1016/j.biomaterials.2010.03.069
Andersen M, Lichawska A, Arpanaei A, Rask Jensen SM, Kaur H, Oupicky D et al. Surface functionalisation of PLGA nanoparticles for gene silencing. Biomaterials. 2010 Jul 1;31(21):5671-5677. https://doi.org/10.1016/j.biomaterials.2010.03.069
Andersen, Morten ; Lichawska, Agata ; Arpanaei, Ayyoob ; Rask Jensen, Stig Møller ; Kaur, Harpreet ; Oupicky, David ; Besenbacher, Flemming ; Kingshott, Peter ; Kjems, Jørgen ; Howard, Kenneth A. / Surface functionalisation of PLGA nanoparticles for gene silencing. In: Biomaterials. 2010 ; Vol. 31, No. 21. pp. 5671-5677.
@article{49f950cb7d904597b9d35b1a7dcc0756,
title = "Surface functionalisation of PLGA nanoparticles for gene silencing",
abstract = "This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5{\%} surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53{\%}) with no cellular toxicity. In addition, particles containing cetylated-PEI achieved 64{\%} silencing of TNFα in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles.",
keywords = "Cetylated PEI, Drug delivery, PLGA, RNAi, SiRNA, Surface modification",
author = "Morten Andersen and Agata Lichawska and Ayyoob Arpanaei and {Rask Jensen}, {Stig M{\o}ller} and Harpreet Kaur and David Oupicky and Flemming Besenbacher and Peter Kingshott and J{\o}rgen Kjems and Howard, {Kenneth A.}",
year = "2010",
month = "7",
day = "1",
doi = "10.1016/j.biomaterials.2010.03.069",
language = "English (US)",
volume = "31",
pages = "5671--5677",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "21",

}

TY - JOUR

T1 - Surface functionalisation of PLGA nanoparticles for gene silencing

AU - Andersen, Morten

AU - Lichawska, Agata

AU - Arpanaei, Ayyoob

AU - Rask Jensen, Stig Møller

AU - Kaur, Harpreet

AU - Oupicky, David

AU - Besenbacher, Flemming

AU - Kingshott, Peter

AU - Kjems, Jørgen

AU - Howard, Kenneth A.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5% surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular toxicity. In addition, particles containing cetylated-PEI achieved 64% silencing of TNFα in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles.

AB - This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5% surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular toxicity. In addition, particles containing cetylated-PEI achieved 64% silencing of TNFα in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles.

KW - Cetylated PEI

KW - Drug delivery

KW - PLGA

KW - RNAi

KW - SiRNA

KW - Surface modification

UR - http://www.scopus.com/inward/record.url?scp=77953025822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953025822&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2010.03.069

DO - 10.1016/j.biomaterials.2010.03.069

M3 - Article

C2 - 20434215

AN - SCOPUS:77953025822

VL - 31

SP - 5671

EP - 5677

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 21

ER -