Phosphatidylserine-targeted bimodal liposomal nanoparticles for in vivo imaging of breast cancer in mice

Liang Zhang, Heling Zhou, Olivier Belzile, Philip Thorpe, Dawen Zhao

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Phosphatidylserine (PS) that is normally constrained to the inner plasma membrane becomes exposed on the surface of endothelial cells (ECs) in tumor vasculature. In the present study, we report the development of a novel tumor vasculature-targeted liposomal nanoprobe by conjugating a human monoclonal antibody, PGN635 that specifically targets PS to polyethylene glycol-coated liposomes. MR contrast, superparamagnetic iron oxide nanoparticles (SPIO) were packed into the core of liposomes, while near-infrared dye, DiR was incorporated into the lipophilic bilayer. The liposomal nanoprobe PGN-L-IO/DiR was fully characterized, and its binding specificity and subsequent internalization into PS-exposed vascular ECs was confirmed by in vitro MRI and histological staining. In vivo longitudinal MRI and optical imaging were performed after i.v. injection of the liposomal nanoprobes into mice bearing breast MDA-MB231 tumors. At 9.4 T, T2-weighted MRI detected drastic reduction on signal intensity and T2 values of tumors at 24 h. Ionizing radiation significantly increased PS exposure on tumor vascular ECs, resulting in a further MRI signal loss of tumors. Concurrent with MRI, optical imaging revealed a clear tumor contrast at 24 h. Intriguingly, PGN-L-IO/DiR exhibited distinct pharmacokinetics and biodistribution with significantly reduced accumulations in liver or spleen. Localization of PGN-L-IO/DiR to tumor was antigen specific, since a control probe of irrelevant specificity showed minimal accumulation in the tumors. Our studies indicate that PS-targeted liposomes may provide a useful platform for tumor-targeted delivery of imaging contrast agents or potentially anti-cancer drugs for cancer theranostics.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalJournal of Controlled Release
Volume183
Issue number1
DOIs
StatePublished - Jun 10 2014

Fingerprint

Phosphatidylserines
Nanoparticles
Breast Neoplasms
Neoplasms
Liposomes
Endothelial Cells
Optical Imaging
Neoplasm Antigens
Ionizing Radiation
Contrast Media
Breast
Coloring Agents
Spleen
Pharmacokinetics
Monoclonal Antibodies
Cell Membrane
Staining and Labeling

Keywords

  • Bimodal liposomal nanoprobe
  • Breast cancer
  • Magnetic resonance imaging (MRI)
  • Near-infrared optical imaging
  • Phosphatidylserine (PS)
  • Tumor vasculature

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

Cite this

Phosphatidylserine-targeted bimodal liposomal nanoparticles for in vivo imaging of breast cancer in mice. / Zhang, Liang; Zhou, Heling; Belzile, Olivier; Thorpe, Philip; Zhao, Dawen.

In: Journal of Controlled Release, Vol. 183, No. 1, 10.06.2014, p. 114-123.

Research output: Contribution to journalArticle

Zhang, Liang ; Zhou, Heling ; Belzile, Olivier ; Thorpe, Philip ; Zhao, Dawen. / Phosphatidylserine-targeted bimodal liposomal nanoparticles for in vivo imaging of breast cancer in mice. In: Journal of Controlled Release. 2014 ; Vol. 183, No. 1. pp. 114-123.
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