Functionalized nanoparticles with targeted antibody to enhance imaging of breast cancer in vivo

J Nanobiotechnology. 2020 Sep 18;18(1):135. doi: 10.1186/s12951-020-00695-2.

Abstract

Background: Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent.

Results: Testing in two mouse tumor models confirms this contrast agent's ability to image HER-2 positive tumors. Intravenous injection of this nanoparticle in mice bearing HER-2 positive mammary tumors significantly enhances MRI signal intensity by ~ 20% and improves CT resolution and contrast by two-fold. Results by flow cytometry and confocal microscopy validate the specific targeting of the conjugate and its internalization in human HER-2 positive cells.

Conclusion: These results demonstrate that this nanoparticle conjugate can efficiently target and image HER-2 positive tumors in vivo and provide a basis for the development of this diagnostic tool for early detection, metastatic assessment and therapeutic monitoring of HER-2 positive cancers.

Keywords: Bi-modal imaging; Computerized tomography; HER-2; Magnetic resonance imaging; Nanoparticles; Targeting.

MeSH terms

  • A549 Cells
  • Animals
  • Antibodies / pharmacology*
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / pathology
  • Drug Delivery Systems
  • Gadolinium
  • Humans
  • Kinetics
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Nanoparticles / chemistry*
  • Receptor, ErbB-2 / immunology*
  • Tomography, X-Ray Computed / methods

Substances

  • Antibodies
  • Gadolinium
  • ERBB2 protein, human
  • Erbb2 protein, mouse
  • Receptor, ErbB-2