Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging

Jinho Park, Sunghyun Kim, Phei Er Saw, In Hyun Lee, Mi Kyung Yu, Minsik Kim, Kwangyeol Lee, Yong Chul Kim, Yong Yeon Jeong, Sangyong Jon

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated blood vessels and extracellular matrix, and thus is a promising cancer biomarker. Very recently, we developed a novel class of high-affinity (< 100 nM) peptides, termed 'aptides', that specifically bind a variety of protein targets. Here, we describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB-specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer. An anti-EDB aptide (APT EDB) containing an additional cysteine residue reacted with maleimide-terminated, PEGylated phospholipid (Mal-PEG2000-DSPE) to give an aptide-conjugated PEGylated phospholipid (APTEDB-PEG 2000-DSPE). A nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with amphiphilic phospholipids, including APT EDB-PEG2000-DSPE, methoxy-PEG2000-DSPE, and rhodamine-DMPE. The resulting nanoparticles (APTEDB-SPIONs) had a hydrodynamic size of less than 50 nm and remained stable in an aqueous solution for at least 1 week. In in vitro studies, APTEDB-SPIONs showed specific uptake by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that expresses a high level of the target EDB protein, MRI clearly revealed that APTEDB-SPIONs injected via the tail vein specifically accumulated at the tumor site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed that the distribution of nanoparticles within the tumor tissue was well correlated with the areas where EDB was expressed. Our APTEDB-SPIONs hold high potential as a specific imaging modality for the detection of EDB-overexpressing tumors.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalJournal of Controlled Release
Volume163
Issue number2
DOIs
Publication statusPublished - 2012 Oct 28

Fingerprint

Fibronectins
Nanoparticles
Neoplasms
Phospholipids
Magnetic Resonance Imaging
Lewis Lung Carcinoma
Rhodamines
Hydrodynamics
Oleic Acid
Tumor Biomarkers
ferric oxide
Extracellular Matrix
Cysteine
Blood Vessels
Veins
Cell Line
Peptides

Keywords

  • Aptide
  • Cancer imaging
  • Fibronectin extra domain
  • MRI
  • SPION

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging. / Park, Jinho; Kim, Sunghyun; Saw, Phei Er; Lee, In Hyun; Yu, Mi Kyung; Kim, Minsik; Lee, Kwangyeol; Kim, Yong Chul; Jeong, Yong Yeon; Jon, Sangyong.

In: Journal of Controlled Release, Vol. 163, No. 2, 28.10.2012, p. 111-118.

Research output: Contribution to journalArticle

Park, J, Kim, S, Saw, PE, Lee, IH, Yu, MK, Kim, M, Lee, K, Kim, YC, Jeong, YY & Jon, S 2012, 'Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging', Journal of Controlled Release, vol. 163, no. 2, pp. 111-118. https://doi.org/10.1016/j.jconrel.2012.08.029
Park, Jinho ; Kim, Sunghyun ; Saw, Phei Er ; Lee, In Hyun ; Yu, Mi Kyung ; Kim, Minsik ; Lee, Kwangyeol ; Kim, Yong Chul ; Jeong, Yong Yeon ; Jon, Sangyong. / Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging. In: Journal of Controlled Release. 2012 ; Vol. 163, No. 2. pp. 111-118.
@article{942251fa04a0494a8ff98a37c5b8e6d7,
title = "Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging",
abstract = "Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated blood vessels and extracellular matrix, and thus is a promising cancer biomarker. Very recently, we developed a novel class of high-affinity (< 100 nM) peptides, termed 'aptides', that specifically bind a variety of protein targets. Here, we describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB-specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer. An anti-EDB aptide (APT EDB) containing an additional cysteine residue reacted with maleimide-terminated, PEGylated phospholipid (Mal-PEG2000-DSPE) to give an aptide-conjugated PEGylated phospholipid (APTEDB-PEG 2000-DSPE). A nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with amphiphilic phospholipids, including APT EDB-PEG2000-DSPE, methoxy-PEG2000-DSPE, and rhodamine-DMPE. The resulting nanoparticles (APTEDB-SPIONs) had a hydrodynamic size of less than 50 nm and remained stable in an aqueous solution for at least 1 week. In in vitro studies, APTEDB-SPIONs showed specific uptake by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that expresses a high level of the target EDB protein, MRI clearly revealed that APTEDB-SPIONs injected via the tail vein specifically accumulated at the tumor site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed that the distribution of nanoparticles within the tumor tissue was well correlated with the areas where EDB was expressed. Our APTEDB-SPIONs hold high potential as a specific imaging modality for the detection of EDB-overexpressing tumors.",
keywords = "Aptide, Cancer imaging, Fibronectin extra domain, MRI, SPION",
author = "Jinho Park and Sunghyun Kim and Saw, {Phei Er} and Lee, {In Hyun} and Yu, {Mi Kyung} and Minsik Kim and Kwangyeol Lee and Kim, {Yong Chul} and Jeong, {Yong Yeon} and Sangyong Jon",
year = "2012",
month = "10",
day = "28",
doi = "10.1016/j.jconrel.2012.08.029",
language = "English",
volume = "163",
pages = "111--118",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging

AU - Park, Jinho

AU - Kim, Sunghyun

AU - Saw, Phei Er

AU - Lee, In Hyun

AU - Yu, Mi Kyung

AU - Kim, Minsik

AU - Lee, Kwangyeol

AU - Kim, Yong Chul

AU - Jeong, Yong Yeon

AU - Jon, Sangyong

PY - 2012/10/28

Y1 - 2012/10/28

N2 - Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated blood vessels and extracellular matrix, and thus is a promising cancer biomarker. Very recently, we developed a novel class of high-affinity (< 100 nM) peptides, termed 'aptides', that specifically bind a variety of protein targets. Here, we describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB-specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer. An anti-EDB aptide (APT EDB) containing an additional cysteine residue reacted with maleimide-terminated, PEGylated phospholipid (Mal-PEG2000-DSPE) to give an aptide-conjugated PEGylated phospholipid (APTEDB-PEG 2000-DSPE). A nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with amphiphilic phospholipids, including APT EDB-PEG2000-DSPE, methoxy-PEG2000-DSPE, and rhodamine-DMPE. The resulting nanoparticles (APTEDB-SPIONs) had a hydrodynamic size of less than 50 nm and remained stable in an aqueous solution for at least 1 week. In in vitro studies, APTEDB-SPIONs showed specific uptake by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that expresses a high level of the target EDB protein, MRI clearly revealed that APTEDB-SPIONs injected via the tail vein specifically accumulated at the tumor site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed that the distribution of nanoparticles within the tumor tissue was well correlated with the areas where EDB was expressed. Our APTEDB-SPIONs hold high potential as a specific imaging modality for the detection of EDB-overexpressing tumors.

AB - Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated blood vessels and extracellular matrix, and thus is a promising cancer biomarker. Very recently, we developed a novel class of high-affinity (< 100 nM) peptides, termed 'aptides', that specifically bind a variety of protein targets. Here, we describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB-specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer. An anti-EDB aptide (APT EDB) containing an additional cysteine residue reacted with maleimide-terminated, PEGylated phospholipid (Mal-PEG2000-DSPE) to give an aptide-conjugated PEGylated phospholipid (APTEDB-PEG 2000-DSPE). A nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with amphiphilic phospholipids, including APT EDB-PEG2000-DSPE, methoxy-PEG2000-DSPE, and rhodamine-DMPE. The resulting nanoparticles (APTEDB-SPIONs) had a hydrodynamic size of less than 50 nm and remained stable in an aqueous solution for at least 1 week. In in vitro studies, APTEDB-SPIONs showed specific uptake by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that expresses a high level of the target EDB protein, MRI clearly revealed that APTEDB-SPIONs injected via the tail vein specifically accumulated at the tumor site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed that the distribution of nanoparticles within the tumor tissue was well correlated with the areas where EDB was expressed. Our APTEDB-SPIONs hold high potential as a specific imaging modality for the detection of EDB-overexpressing tumors.

KW - Aptide

KW - Cancer imaging

KW - Fibronectin extra domain

KW - MRI

KW - SPION

UR - http://www.scopus.com/inward/record.url?scp=84866555295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866555295&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2012.08.029

DO - 10.1016/j.jconrel.2012.08.029

M3 - Article

C2 - 22964395

AN - SCOPUS:84866555295

VL - 163

SP - 111

EP - 118

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 2

ER -