Targeted therapy of triple negative MDA‑MB‑468 breast cancer with curcumin delivered by epidermal growth factor‑conjugated phospholipid nanoparticles

Jung,Kyung‑Ho; Lee,Jin  Hee; Park,Jin  Won; Kim,Da  Hae; Moon,Seung‑Hwan; Cho,Young  Seok; Lee,Kyung‑Han

doi:10.3892/ol.2018.8471

Targeted therapy of triple negative MDA‑MB‑468 breast cancer with curcumin delivered by epidermal growth factor‑conjugated phospholipid nanoparticles

Authors:
- Kyung‑Ho Jung
- Jin Hee Lee
- Jin Won Park
- Da Hae Kim
- Seung‑Hwan Moon
- Young Seok Cho
- Kyung‑Han Lee
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Affiliations: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
Published online on: April 12, 2018 https://doi.org/10.3892/ol.2018.8471
Pages: 9093-9100
Copyright: © Jung et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Triple‑negative breast cancer (TNBC) is associated with poor survival as chemotherapy is currently limited to conventional cytotoxic agents. Curcumin has promising anticancer actions against TNBC, but its application is hindered by poor bioavailability and rapid degradation in vivo. In the present study, curcumin‑loaded phospholipid nanoparticles (Cur‑NPs) conjugated with epidermal growth factor (EGF) were prepared for specific targeting of EGF receptors overexpressed in TNBC. NP formulation was performed by reacting EGF peptide with N‑hydroxysuccinimide-Polyethylene Glycol-1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (NHS-PEG10000-DSPE), followed by efficient curcumin loading through lipid film hydration. EGF conjugation did not significantly affect NP size, zeta potential or morphology. Specific targeting was confirmed by EGF receptor activation and blocking of 125I‑labeled NP binding by excess EGF. EGF‑Cur‑NP dose‑dependently suppressed MDA‑MB‑468 TNBC cell survival (IC50, 620 nM), and completely abolished their capacity to form colonies. The cytotoxic effects were more potent compared with those of free curcumin or Cur‑NP. In mice bearing MDA‑MB‑468 tumors, injections of 10 mg/kg EGF‑Cur‑NP caused a 59.1% retardation of tumor growth at 3 weeks compared with empty NP, whereas the antitumor effect of Cur‑NP was weak. These results indicate that EGF‑conjugated NHS‑PEG10000‑DSPE phospholipid NPs loaded with curcumin may be useful for treating TNBCs that overexpress the EGF receptor.

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