Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer

Daniel J. Toft, Tyson J. Moyer, Stephany M. Standley, Yves Ruff, Andrey Ugolkov, Samuel I Stupp, Vincent L. Cryns

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Self-assembled peptide amphiphiles (PAs) consisting of hydrophobic, hydvrogen-bonding, and charged hydrophilic domains form cylindrical nanofibers in physiological conditions and allow for the presentation of a high density of bioactive epitopes on the nanofiber surface. We report here on the use of PAs to form multifunctional nanostructures with tumoricidal activity. The combination of a cationic, membrane-lytic PA coassembled with a serum-protective, pegylated PA was shown to self-assemble into nanofibers. Addition of the pegylated PA to the nanostructure substantially limited degradation of the cytolytic PA by the protease trypsin, with an 8-fold increase in the amount of intact PA observed after digestion. At the same time, addition of up to 50% pegylated PA to the nanofibers did not decrease the in vitro cytotoxicity of the cytolytic PA. Using a fluorescent tag covalently attached to PA nanofibers we were able to track the biodistribution in plasma and tissues of tumor-bearing mice over time after intraperitoneal administration of the nanoscale filaments. Using an orthotopic mouse xenograft model of breast cancer, systemic administration of the cytotoxic pegylated nanostructures significantly reduced tumor cell proliferation and overall tumor growth, demonstrating the potential of multifunctional PA nanostructures as versatile cancer therapeutics.

Original languageEnglish
Pages (from-to)7956-7965
Number of pages10
JournalACS Nano
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 25 2012

Fingerprint

Amphiphiles
breast
Peptides
peptides
Nanostructures
cancer
Nanofibers
Tumors
tumors
mice
Bearings (structural)
Epitopes
trypsin
protease
Cell proliferation
Cytotoxicity
activity (biology)
Heterografts
serums
Trypsin

Keywords

  • breast cancer
  • cancer therapy
  • nanofiber
  • pegylation
  • peptide amphiphile

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer. / Toft, Daniel J.; Moyer, Tyson J.; Standley, Stephany M.; Ruff, Yves; Ugolkov, Andrey; Stupp, Samuel I; Cryns, Vincent L.

In: ACS Nano, Vol. 6, No. 9, 25.09.2012, p. 7956-7965.

Research output: Contribution to journalArticle

Toft, Daniel J. ; Moyer, Tyson J. ; Standley, Stephany M. ; Ruff, Yves ; Ugolkov, Andrey ; Stupp, Samuel I ; Cryns, Vincent L. / Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer. In: ACS Nano. 2012 ; Vol. 6, No. 9. pp. 7956-7965.
@article{a4129b8639b84063813e66fe59f744b1,
title = "Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer",
abstract = "Self-assembled peptide amphiphiles (PAs) consisting of hydrophobic, hydvrogen-bonding, and charged hydrophilic domains form cylindrical nanofibers in physiological conditions and allow for the presentation of a high density of bioactive epitopes on the nanofiber surface. We report here on the use of PAs to form multifunctional nanostructures with tumoricidal activity. The combination of a cationic, membrane-lytic PA coassembled with a serum-protective, pegylated PA was shown to self-assemble into nanofibers. Addition of the pegylated PA to the nanostructure substantially limited degradation of the cytolytic PA by the protease trypsin, with an 8-fold increase in the amount of intact PA observed after digestion. At the same time, addition of up to 50{\%} pegylated PA to the nanofibers did not decrease the in vitro cytotoxicity of the cytolytic PA. Using a fluorescent tag covalently attached to PA nanofibers we were able to track the biodistribution in plasma and tissues of tumor-bearing mice over time after intraperitoneal administration of the nanoscale filaments. Using an orthotopic mouse xenograft model of breast cancer, systemic administration of the cytotoxic pegylated nanostructures significantly reduced tumor cell proliferation and overall tumor growth, demonstrating the potential of multifunctional PA nanostructures as versatile cancer therapeutics.",
keywords = "breast cancer, cancer therapy, nanofiber, pegylation, peptide amphiphile",
author = "Toft, {Daniel J.} and Moyer, {Tyson J.} and Standley, {Stephany M.} and Yves Ruff and Andrey Ugolkov and Stupp, {Samuel I} and Cryns, {Vincent L.}",
year = "2012",
month = "9",
day = "25",
doi = "10.1021/nn302503s",
language = "English",
volume = "6",
pages = "7956--7965",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer

AU - Toft, Daniel J.

AU - Moyer, Tyson J.

AU - Standley, Stephany M.

AU - Ruff, Yves

AU - Ugolkov, Andrey

AU - Stupp, Samuel I

AU - Cryns, Vincent L.

PY - 2012/9/25

Y1 - 2012/9/25

N2 - Self-assembled peptide amphiphiles (PAs) consisting of hydrophobic, hydvrogen-bonding, and charged hydrophilic domains form cylindrical nanofibers in physiological conditions and allow for the presentation of a high density of bioactive epitopes on the nanofiber surface. We report here on the use of PAs to form multifunctional nanostructures with tumoricidal activity. The combination of a cationic, membrane-lytic PA coassembled with a serum-protective, pegylated PA was shown to self-assemble into nanofibers. Addition of the pegylated PA to the nanostructure substantially limited degradation of the cytolytic PA by the protease trypsin, with an 8-fold increase in the amount of intact PA observed after digestion. At the same time, addition of up to 50% pegylated PA to the nanofibers did not decrease the in vitro cytotoxicity of the cytolytic PA. Using a fluorescent tag covalently attached to PA nanofibers we were able to track the biodistribution in plasma and tissues of tumor-bearing mice over time after intraperitoneal administration of the nanoscale filaments. Using an orthotopic mouse xenograft model of breast cancer, systemic administration of the cytotoxic pegylated nanostructures significantly reduced tumor cell proliferation and overall tumor growth, demonstrating the potential of multifunctional PA nanostructures as versatile cancer therapeutics.

AB - Self-assembled peptide amphiphiles (PAs) consisting of hydrophobic, hydvrogen-bonding, and charged hydrophilic domains form cylindrical nanofibers in physiological conditions and allow for the presentation of a high density of bioactive epitopes on the nanofiber surface. We report here on the use of PAs to form multifunctional nanostructures with tumoricidal activity. The combination of a cationic, membrane-lytic PA coassembled with a serum-protective, pegylated PA was shown to self-assemble into nanofibers. Addition of the pegylated PA to the nanostructure substantially limited degradation of the cytolytic PA by the protease trypsin, with an 8-fold increase in the amount of intact PA observed after digestion. At the same time, addition of up to 50% pegylated PA to the nanofibers did not decrease the in vitro cytotoxicity of the cytolytic PA. Using a fluorescent tag covalently attached to PA nanofibers we were able to track the biodistribution in plasma and tissues of tumor-bearing mice over time after intraperitoneal administration of the nanoscale filaments. Using an orthotopic mouse xenograft model of breast cancer, systemic administration of the cytotoxic pegylated nanostructures significantly reduced tumor cell proliferation and overall tumor growth, demonstrating the potential of multifunctional PA nanostructures as versatile cancer therapeutics.

KW - breast cancer

KW - cancer therapy

KW - nanofiber

KW - pegylation

KW - peptide amphiphile

UR - http://www.scopus.com/inward/record.url?scp=84866635545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866635545&partnerID=8YFLogxK

U2 - 10.1021/nn302503s

DO - 10.1021/nn302503s

M3 - Article

C2 - 22928955

AN - SCOPUS:84866635545

VL - 6

SP - 7956

EP - 7965

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 9

ER -