An affinity triggered MRI nanoprobe for pH-dependent cell labeling

Susana I. C. J. Palma, Alexandra R. Fernandes, Ana C A Roque

Research output: Contribution to journalArticle

Abstract

The pH-sensitive affinity pair composed by neutravidin and iminobiotin was used to develop a multilayered Magnetic Resonance Imaging (MRI) nanoprobe responsive to the acidic pH of tumor microenvironment. The multilayer system was assembled on meso-2,3-dimercaptosuccinic acid-coated iron oxide magnetic nanoparticles (MNP), which convey negative MRI contrast enhancement properties to the nanoprobe. The outer stealth PEG-layer is altered in acidic media due to the disruption of interactions between neutravidin-iminobiotin. As a consequence, the positively charged inner layer is exposed and enhances interactions with cells. The nanoprobe uptake by HCT116 cells cultured in vitro under acidic conditions had a 2-fold increase compared to the uptake at physiological pH. The uptake difference is particularly clear in T2-weighted MRI phantoms of cells incubated with the nanoprobes at both pH conditions. This work sets the proof-of-concept of a MNP-based MRI nanoprobe targeting acidic tumor microenvironment through the use of a specific bio-recognition interaction that is pH-sensitive. This tumor targeting strategy is potentially applicable to the generality of tumors since the typical hypoxic conditions and high glycolysis rate in cancer cells create an acidic environment common to the majority of cancer types.

Original languageEnglish
Pages (from-to)113503-113512
Number of pages10
JournalRCS Advances
Volume6
Issue number114
DOIs
Publication statusPublished - 2016

Fingerprint

Nanoprobes
Labeling
Tumors
Succimer
Nanoparticles
Iron oxides
Polyethylene glycols
Multilayers
Cells
Magnetic Resonance Imaging
Acids

Keywords

  • SUPERPARAMAGNETIC IRON-OXIDE
  • COATED MAGNETIC NANOPARTICLES
  • ASSEMBLED NANOPARTICLES
  • BIOMEDICAL APPLICATIONS
  • POLYETHYLENE-GLYCOL
  • DRUG-DELIVERY
  • CANCER-CELLS
  • IN-VITRO
  • THERAPY
  • BIODISTRIBUTION

Cite this

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title = "An affinity triggered MRI nanoprobe for pH-dependent cell labeling",
abstract = "The pH-sensitive affinity pair composed by neutravidin and iminobiotin was used to develop a multilayered Magnetic Resonance Imaging (MRI) nanoprobe responsive to the acidic pH of tumor microenvironment. The multilayer system was assembled on meso-2,3-dimercaptosuccinic acid-coated iron oxide magnetic nanoparticles (MNP), which convey negative MRI contrast enhancement properties to the nanoprobe. The outer stealth PEG-layer is altered in acidic media due to the disruption of interactions between neutravidin-iminobiotin. As a consequence, the positively charged inner layer is exposed and enhances interactions with cells. The nanoprobe uptake by HCT116 cells cultured in vitro under acidic conditions had a 2-fold increase compared to the uptake at physiological pH. The uptake difference is particularly clear in T2-weighted MRI phantoms of cells incubated with the nanoprobes at both pH conditions. This work sets the proof-of-concept of a MNP-based MRI nanoprobe targeting acidic tumor microenvironment through the use of a specific bio-recognition interaction that is pH-sensitive. This tumor targeting strategy is potentially applicable to the generality of tumors since the typical hypoxic conditions and high glycolysis rate in cancer cells create an acidic environment common to the majority of cancer types.",
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author = "Palma, {Susana I. C. J.} and Fernandes, {Alexandra R.} and Roque, {Ana C A}",
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An affinity triggered MRI nanoprobe for pH-dependent cell labeling. / Palma, Susana I. C. J.; Fernandes, Alexandra R.; Roque, Ana C A.

In: RCS Advances, Vol. 6, No. 114, 2016, p. 113503-113512.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An affinity triggered MRI nanoprobe for pH-dependent cell labeling

AU - Palma, Susana I. C. J.

AU - Fernandes, Alexandra R.

AU - Roque, Ana C A

N1 - Sem PDF. Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO FCT/MEC (UID/Multi/04378/2013) ERDF (POCI-01-0145-FEDER-007728) Fundacao para a Ciencia e Tecnologia (FCT) (SFRH/BD/51112/2010; PTDC/EBB-BIO/118317/2010; PTDC/BBB-NAN/1812/2012)

PY - 2016

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N2 - The pH-sensitive affinity pair composed by neutravidin and iminobiotin was used to develop a multilayered Magnetic Resonance Imaging (MRI) nanoprobe responsive to the acidic pH of tumor microenvironment. The multilayer system was assembled on meso-2,3-dimercaptosuccinic acid-coated iron oxide magnetic nanoparticles (MNP), which convey negative MRI contrast enhancement properties to the nanoprobe. The outer stealth PEG-layer is altered in acidic media due to the disruption of interactions between neutravidin-iminobiotin. As a consequence, the positively charged inner layer is exposed and enhances interactions with cells. The nanoprobe uptake by HCT116 cells cultured in vitro under acidic conditions had a 2-fold increase compared to the uptake at physiological pH. The uptake difference is particularly clear in T2-weighted MRI phantoms of cells incubated with the nanoprobes at both pH conditions. This work sets the proof-of-concept of a MNP-based MRI nanoprobe targeting acidic tumor microenvironment through the use of a specific bio-recognition interaction that is pH-sensitive. This tumor targeting strategy is potentially applicable to the generality of tumors since the typical hypoxic conditions and high glycolysis rate in cancer cells create an acidic environment common to the majority of cancer types.

AB - The pH-sensitive affinity pair composed by neutravidin and iminobiotin was used to develop a multilayered Magnetic Resonance Imaging (MRI) nanoprobe responsive to the acidic pH of tumor microenvironment. The multilayer system was assembled on meso-2,3-dimercaptosuccinic acid-coated iron oxide magnetic nanoparticles (MNP), which convey negative MRI contrast enhancement properties to the nanoprobe. The outer stealth PEG-layer is altered in acidic media due to the disruption of interactions between neutravidin-iminobiotin. As a consequence, the positively charged inner layer is exposed and enhances interactions with cells. The nanoprobe uptake by HCT116 cells cultured in vitro under acidic conditions had a 2-fold increase compared to the uptake at physiological pH. The uptake difference is particularly clear in T2-weighted MRI phantoms of cells incubated with the nanoprobes at both pH conditions. This work sets the proof-of-concept of a MNP-based MRI nanoprobe targeting acidic tumor microenvironment through the use of a specific bio-recognition interaction that is pH-sensitive. This tumor targeting strategy is potentially applicable to the generality of tumors since the typical hypoxic conditions and high glycolysis rate in cancer cells create an acidic environment common to the majority of cancer types.

KW - SUPERPARAMAGNETIC IRON-OXIDE

KW - COATED MAGNETIC NANOPARTICLES

KW - ASSEMBLED NANOPARTICLES

KW - BIOMEDICAL APPLICATIONS

KW - POLYETHYLENE-GLYCOL

KW - DRUG-DELIVERY

KW - CANCER-CELLS

KW - IN-VITRO

KW - THERAPY

KW - BIODISTRIBUTION

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U2 - 10.1039/C6RA17217B

DO - 10.1039/C6RA17217B

M3 - Article

VL - 6

SP - 113503

EP - 113512

JO - RCS Advances

JF - RCS Advances

SN - 2046-2069

IS - 114

ER -