HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy

Jinho Park, Seho Park, Sunghyun Kim, In Hyun Lee, Phei Er Saw, Kwangyeol Lee, Yong Chul Kim, Young Joon Kim, Omid C. Farokhzad, Yong Yeon Jeong, Sangyong Jon

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Here, we report a nanotheranostic system that enables simultaneous imaging and therapy of HER2-overexpressing tumors. We first screened an aptide-based phage library for HER2-specific peptide ligands, identifying a HER2-specific aptide (APTHER2) phage clone. Chemically synthesized APT HER2 showed high affinity for its target protein (Kd ≈ 89 nM) and specifically bound HER2-overexpressing cells (NIH3T6.7) and tumor tissue slices. Next, we prepared HER2-specific-aptide-conjugated magneto-nanoclusters (APTHER2-MNCs) by a rehydration method using oleic acid-stabilized superparamagnetic iron oxide nanoparticles (SPIONs) and amphiphilic phospholipids, yielding nanoparticles with a hydrodynamic diameter of 47 ± 10 nm. The APTHER2-MNCs showed higher transverse (r2) relaxivity (∼180 mM-1 s-1) and greater drug-loading capacity compared to the equivalent isolated SPIONs (∼120 mM-1 s-1). When intravenously injected into HER2-overexpressing NIH3T6.7 tumor-bearing mice, APTHER2-MNCs substantially accumulated in tumor tissue, enhancing the relative signal by ∼45% at 3 h post-injection. This allowed us to detect the tumor using magnetic resonance imaging. Furthermore, after docetaxel loading, the drug-loaded APTHER2-MNCs remarkably inhibited the growth of HER2-overexpressing tumors (∼50% relative to controls) with little apparent toxicity, measured as changes in body weight. Together, these results indicate that APTHER2-MNCs show promise as an efficient nanotheranostic system that enables specific cancer imaging as well as targeted therapy.

Original languageEnglish
Pages (from-to)4576-4583
Number of pages8
JournalJournal of Materials Chemistry B
Volume1
Issue number36
DOIs
Publication statusPublished - 2013 Sep 28

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Nanoclusters
Tumors
Breast Neoplasms
Imaging techniques
Neoplasms
Bacteriophages
Nanoparticles
docetaxel
Iron oxides
Bearings (structural)
Therapeutics
Tissue
Oleic acid
Phospholipids
Magnetic resonance
Oleic Acid
Body Weight Changes
Fluid Therapy
Pharmaceutical Preparations
Peptides

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Medicine(all)
  • Materials Science(all)

Cite this

HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy. / Park, Jinho; Park, Seho; Kim, Sunghyun; Lee, In Hyun; Saw, Phei Er; Lee, Kwangyeol; Kim, Yong Chul; Kim, Young Joon; Farokhzad, Omid C.; Jeong, Yong Yeon; Jon, Sangyong.

In: Journal of Materials Chemistry B, Vol. 1, No. 36, 28.09.2013, p. 4576-4583.

Research output: Contribution to journalArticle

Park, J, Park, S, Kim, S, Lee, IH, Saw, PE, Lee, K, Kim, YC, Kim, YJ, Farokhzad, OC, Jeong, YY & Jon, S 2013, 'HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy', Journal of Materials Chemistry B, vol. 1, no. 36, pp. 4576-4583. https://doi.org/10.1039/c3tb20613k
Park, Jinho ; Park, Seho ; Kim, Sunghyun ; Lee, In Hyun ; Saw, Phei Er ; Lee, Kwangyeol ; Kim, Yong Chul ; Kim, Young Joon ; Farokhzad, Omid C. ; Jeong, Yong Yeon ; Jon, Sangyong. / HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy. In: Journal of Materials Chemistry B. 2013 ; Vol. 1, No. 36. pp. 4576-4583.
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AU - Park, Jinho

AU - Park, Seho

AU - Kim, Sunghyun

AU - Lee, In Hyun

AU - Saw, Phei Er

AU - Lee, Kwangyeol

AU - Kim, Yong Chul

AU - Kim, Young Joon

AU - Farokhzad, Omid C.

AU - Jeong, Yong Yeon

AU - Jon, Sangyong

PY - 2013/9/28

Y1 - 2013/9/28

N2 - Here, we report a nanotheranostic system that enables simultaneous imaging and therapy of HER2-overexpressing tumors. We first screened an aptide-based phage library for HER2-specific peptide ligands, identifying a HER2-specific aptide (APTHER2) phage clone. Chemically synthesized APT HER2 showed high affinity for its target protein (Kd ≈ 89 nM) and specifically bound HER2-overexpressing cells (NIH3T6.7) and tumor tissue slices. Next, we prepared HER2-specific-aptide-conjugated magneto-nanoclusters (APTHER2-MNCs) by a rehydration method using oleic acid-stabilized superparamagnetic iron oxide nanoparticles (SPIONs) and amphiphilic phospholipids, yielding nanoparticles with a hydrodynamic diameter of 47 ± 10 nm. The APTHER2-MNCs showed higher transverse (r2) relaxivity (∼180 mM-1 s-1) and greater drug-loading capacity compared to the equivalent isolated SPIONs (∼120 mM-1 s-1). When intravenously injected into HER2-overexpressing NIH3T6.7 tumor-bearing mice, APTHER2-MNCs substantially accumulated in tumor tissue, enhancing the relative signal by ∼45% at 3 h post-injection. This allowed us to detect the tumor using magnetic resonance imaging. Furthermore, after docetaxel loading, the drug-loaded APTHER2-MNCs remarkably inhibited the growth of HER2-overexpressing tumors (∼50% relative to controls) with little apparent toxicity, measured as changes in body weight. Together, these results indicate that APTHER2-MNCs show promise as an efficient nanotheranostic system that enables specific cancer imaging as well as targeted therapy.

AB - Here, we report a nanotheranostic system that enables simultaneous imaging and therapy of HER2-overexpressing tumors. We first screened an aptide-based phage library for HER2-specific peptide ligands, identifying a HER2-specific aptide (APTHER2) phage clone. Chemically synthesized APT HER2 showed high affinity for its target protein (Kd ≈ 89 nM) and specifically bound HER2-overexpressing cells (NIH3T6.7) and tumor tissue slices. Next, we prepared HER2-specific-aptide-conjugated magneto-nanoclusters (APTHER2-MNCs) by a rehydration method using oleic acid-stabilized superparamagnetic iron oxide nanoparticles (SPIONs) and amphiphilic phospholipids, yielding nanoparticles with a hydrodynamic diameter of 47 ± 10 nm. The APTHER2-MNCs showed higher transverse (r2) relaxivity (∼180 mM-1 s-1) and greater drug-loading capacity compared to the equivalent isolated SPIONs (∼120 mM-1 s-1). When intravenously injected into HER2-overexpressing NIH3T6.7 tumor-bearing mice, APTHER2-MNCs substantially accumulated in tumor tissue, enhancing the relative signal by ∼45% at 3 h post-injection. This allowed us to detect the tumor using magnetic resonance imaging. Furthermore, after docetaxel loading, the drug-loaded APTHER2-MNCs remarkably inhibited the growth of HER2-overexpressing tumors (∼50% relative to controls) with little apparent toxicity, measured as changes in body weight. Together, these results indicate that APTHER2-MNCs show promise as an efficient nanotheranostic system that enables specific cancer imaging as well as targeted therapy.

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