GE11 Modified PLGA/TPGS Nanoparticles Targeting Delivery of Salinomycin to Breast Cancer Cells

Abstract

Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both in vitro and in vivo. Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.

Keywords: GE11; breast cancer; nanoparticles; salinomycin; targeting delivery.

Figure 1.

Characterization of nanoparticles (PLGA/TPGS). Size distribution (A) and zeta potential of nanoparticles (B), as detected by dynamic light scattering. The TEM image of nanoparticles (C). Scale bar:100 nm. One representative image is shown. Data are presented as means ± standard deviations (n = 3).

Figure 2.

GE11 modified nanoparticle targeting to breast cancer cells MCF-7. (A) In vitro cellular uptake analysis in MCF-7 cells were treated with the NP-SAL or NP-SAL-TP nanoparticles for 24 h. After then, the cells were trypsinized, washed and the mean fluorescence intensity was determined by flow cytometry. (B) Quantification of the mean fluorescence intensity with different groups. Data represented as mean ± SD (n = 3). *P < 0.01.

Figure 3.

Suppression of the migration of breast cancer cell MCF-7. (A) The amount of migrating MCF-7 cells markedly suppressed with the targeting nanoparticles. Cells at the lower of the members are stained and images shown here. (B) Quantification of the migrating MCF-7 cells with different groups. *P < 0.05.

Figure 4.

The concentration-dependent cytotoxicity induced by particles in MCF-7 cells after 24 h (A) or 72 h (B). The cells were incubated with varying concentrations of different groups, and the cell viability was determined by CCK-8 assays. Data are presented as means ± standard deviations (n = 3). *P < 0.05.

Figure 5.

Antitumor assay in mice bearing subcutaneous MCF-7 tumors in vivo. (A) Pictures of excised tumors of each group at the end of experiment. (B) Variation in body weight. (C) Tumor growth volume. (D) The excised tumors were weighed at the end point. The 2 groups were compared by 1-way ANOVA with the Newman–Keuls method. Data are expressed as mean ± SD (n = 5). *P < 0.05.