Abstract

Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.

Highlights

  • CD44 is a cell-surface glycoprotein antigen of breast cancer cells that is well known for its specific binding with hyaluronic acid (HA) [1,2,3]

  • Characterization of aminated polysorbate 80 (P80) MnFe2O4 nanocrystals (MNCs), soluble in non-polar organic solvent with high monodispersity, were made using the thermal decomposition method to serve as magnetic resonance (MR) contrast agents

  • The characteristic bands of aminated P80 were verified by FT-IR spectra, which represented N-H stretching of an amine group (3,550 cm−1), C-N stretching of an amide group (3,400 cm−1), and N-H bending of an amine group (1,600 cm−1) (Additional file 1: Figure S1)

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Summary

Introduction

CD44 is a cell-surface glycoprotein antigen of breast cancer cells that is well known for its specific binding with hyaluronic acid (HA) [1,2,3]. It is the multifunctional cell-surface molecule involved in pathologic properties of cancer cells such as cell proliferation, differentiation, migration, angiogenesis, and chemokines [4,5,6]. For sensitive and specific detection of cancer via the CD44 receptor, molecular imaging has been strongly considered due to the accurate acquisition of highly sensitive images and deeper insight into in vivo conditions [15,16,17]. CD44targeted MR imaging has been applied in the treatment of cancer such as monitoring therapeutic efficacy and determining the progonosis of cancer

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