Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery

Aristides Tagalakis, D.H. Lee, A.S. Bienemann, H Zhou, M.M. Munye, L Saraiva, D McCarthy, Z Du, C.A. Vink, R Maeshima, E.A. White, K Gustafsson, S.L. Hart

Research output: Contribution to journalArticle

38 Citations (Scopus)
9 Downloads (Pure)

Abstract

ormulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein.
Original languageEnglish
Pages (from-to)8406-8415
Number of pages10
JournalBiomaterials
Volume35
Issue number29
Early online date28 Jun 2014
DOIs
Publication statusPublished - Sep 2014

Fingerprint

Nanoparticles
Lipids
Peptides
Small Interfering RNA
Liposomes
Transfection
Proteins
Convection
Amyloid Plaques
Gene Silencing
RNA Interference
Coulomb interactions
Static Electricity
RNA
Amyloid
Self assembly
Toxicity
Rats
Blood Proteins
Brain

Keywords

  • Anionic liposome
  • Gene silencing
  • Gene therapy
  • Nanoparticle
  • SiRNA
  • Targeted

Cite this

Tagalakis, A., Lee, D. H., Bienemann, A. S., Zhou, H., Munye, M. M., Saraiva, L., ... Hart, S. L. (2014). Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery. Biomaterials, 35(29), 8406-8415. https://doi.org/10.1016/j.biomaterials.2014.06.003
Tagalakis, Aristides ; Lee, D.H. ; Bienemann, A.S. ; Zhou, H ; Munye, M.M. ; Saraiva, L ; McCarthy, D ; Du, Z ; Vink, C.A. ; Maeshima, R ; White, E.A. ; Gustafsson, K ; Hart, S.L. / Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery. In: Biomaterials. 2014 ; Vol. 35, No. 29. pp. 8406-8415.
@article{1233908a0fb9481d910e9e4120d9b1e2,
title = "Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery",
abstract = "ormulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein.",
keywords = "Anionic liposome, Gene silencing, Gene therapy, Nanoparticle, SiRNA, Targeted",
author = "Aristides Tagalakis and D.H. Lee and A.S. Bienemann and H Zhou and M.M. Munye and L Saraiva and D McCarthy and Z Du and C.A. Vink and R Maeshima and E.A. White and K Gustafsson and S.L. Hart",
year = "2014",
month = "9",
doi = "10.1016/j.biomaterials.2014.06.003",
language = "English",
volume = "35",
pages = "8406--8415",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",
number = "29",

}

Tagalakis, A, Lee, DH, Bienemann, AS, Zhou, H, Munye, MM, Saraiva, L, McCarthy, D, Du, Z, Vink, CA, Maeshima, R, White, EA, Gustafsson, K & Hart, SL 2014, 'Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery', Biomaterials, vol. 35, no. 29, pp. 8406-8415. https://doi.org/10.1016/j.biomaterials.2014.06.003

Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery. / Tagalakis, Aristides; Lee, D.H.; Bienemann, A.S.; Zhou, H; Munye, M.M.; Saraiva, L; McCarthy, D; Du, Z; Vink, C.A.; Maeshima, R; White, E.A.; Gustafsson, K; Hart, S.L.

In: Biomaterials, Vol. 35, No. 29, 09.2014, p. 8406-8415.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery

AU - Tagalakis, Aristides

AU - Lee, D.H.

AU - Bienemann, A.S.

AU - Zhou, H

AU - Munye, M.M.

AU - Saraiva, L

AU - McCarthy, D

AU - Du, Z

AU - Vink, C.A.

AU - Maeshima, R

AU - White, E.A.

AU - Gustafsson, K

AU - Hart, S.L.

PY - 2014/9

Y1 - 2014/9

N2 - ormulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein.

AB - ormulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein.

KW - Anionic liposome

KW - Gene silencing

KW - Gene therapy

KW - Nanoparticle

KW - SiRNA

KW - Targeted

UR - http://www.mendeley.com/research/multifunctional-selfassembling-anionic-peptidelipid-nanocomplexes-targeted-sirna-delivery

U2 - 10.1016/j.biomaterials.2014.06.003

DO - 10.1016/j.biomaterials.2014.06.003

M3 - Article

VL - 35

SP - 8406

EP - 8415

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 29

ER -