Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment

Lígia C. Gomes-da-Silva, Adriana O. Santos, Luís M. Bimbo, Vera Moura, José S. Ramalho, Maria C. Pedroso de Lima, Sérgio Simões, João N. Moreira

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The present work aimed at designing a lipid-based nanocarrier for siRNA delivery toward two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non-cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co-localization studies between the siRNA and the lysosomes. Overall, the present work represents an important contribution toward a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level.

LanguageEnglish
Pages9-19
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume434
Issue number1-2
Early online date19 May 2012
DOIs
Publication statusPublished - 15 Sep 2012
Externally publishedYes

Fingerprint

Cellular Microenvironment
Tumor Microenvironment
Nanoparticles
Small Interfering RNA
Breast Neoplasms
Endothelial Cells
Vascular Tissue Neoplasms
Lipids
Peptides
Ethylene Glycol
Lysosomes
Liposomes
Nucleic Acids
Population
Blood Vessels
Neoplasms
Down-Regulation
Cell Line
Messenger RNA
enhanced green fluorescent protein

Keywords

  • breast neoplasms
  • down-regulation
  • endothelial cells
  • green fluorescent proteins
  • humans
  • liposomes
  • lysosomes
  • nanoparticles
  • neovascularization, pathologic
  • peptides
  • phosphoproteins
  • polyethylene glycols
  • RNA, messenger
  • RNA, small interfering
  • RNA-binding proteins
  • tumor microenvironment

Cite this

Gomes-da-Silva, L. C., Santos, A. O., Bimbo, L. M., Moura, V., Ramalho, J. S., Pedroso de Lima, M. C., ... Moreira, J. N. (2012). Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment. International Journal of Pharmaceutics, 434(1-2), 9-19. https://doi.org/10.1016/j.ijpharm.2012.05.018
Gomes-da-Silva, Lígia C. ; Santos, Adriana O. ; Bimbo, Luís M. ; Moura, Vera ; Ramalho, José S. ; Pedroso de Lima, Maria C. ; Simões, Sérgio ; Moreira, João N. / Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment. In: International Journal of Pharmaceutics. 2012 ; Vol. 434, No. 1-2. pp. 9-19.
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Gomes-da-Silva, LC, Santos, AO, Bimbo, LM, Moura, V, Ramalho, JS, Pedroso de Lima, MC, Simões, S & Moreira, JN 2012, 'Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment' International Journal of Pharmaceutics, vol. 434, no. 1-2, pp. 9-19. https://doi.org/10.1016/j.ijpharm.2012.05.018

Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment. / Gomes-da-Silva, Lígia C.; Santos, Adriana O.; Bimbo, Luís M.; Moura, Vera; Ramalho, José S.; Pedroso de Lima, Maria C.; Simões, Sérgio; Moreira, João N.

In: International Journal of Pharmaceutics, Vol. 434, No. 1-2, 15.09.2012, p. 9-19.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Toward a siRNA-containing nanoparticle targeted to breast cancer cells and the tumor microenvironment

AU - Gomes-da-Silva, Lígia C.

AU - Santos, Adriana O.

AU - Bimbo, Luís M.

AU - Moura, Vera

AU - Ramalho, José S.

AU - Pedroso de Lima, Maria C.

AU - Simões, Sérgio

AU - Moreira, João N.

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Y1 - 2012/9/15

N2 - The present work aimed at designing a lipid-based nanocarrier for siRNA delivery toward two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non-cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co-localization studies between the siRNA and the lysosomes. Overall, the present work represents an important contribution toward a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level.

AB - The present work aimed at designing a lipid-based nanocarrier for siRNA delivery toward two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic acid lipid particles presented adequate features for systemic administration. In addition, the attachment of the F3 peptide onto the liposomal surface enabled an internalization by both cancer and endothelial cells from angiogenic blood vessels that was significantly higher than the one observed with non-cancer cells. Sequence-specific downregulation of enhanced green fluorescent protein (eGFP) in eGFP-overexpressing human cancer cell lines, both at the protein and mRNA levels, was further observed upon delivery of anti-eGFP siRNA by F3-targeted liposomes, in contrast with the non-targeted counterpart. This effect was highly dependent on the content of poly(ethylene glycol) (PEG), as evidenced by the co-localization studies between the siRNA and the lysosomes. Overall, the present work represents an important contribution toward a nanoparticle with multi-targeting capabilities in breast cancer, both at the cellular and molecular level.

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KW - down-regulation

KW - endothelial cells

KW - green fluorescent proteins

KW - humans

KW - liposomes

KW - lysosomes

KW - nanoparticles

KW - neovascularization, pathologic

KW - peptides

KW - phosphoproteins

KW - polyethylene glycols

KW - RNA, messenger

KW - RNA, small interfering

KW - RNA-binding proteins

KW - tumor microenvironment

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T2 - International Journal of Pharmaceutics

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