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. 2017 Feb 8;7(4):899-911.
doi: 10.7150/thno.17927. eCollection 2017.

Incorporating gold nanoclusters and target-directed liposomes as a synergistic amplified colorimetric sensor for HER2-positive breast cancer cell detection

Yu Tao  1 , Mingqiang Li  2 , Bumjun Kim  1 , Debra T Auguste  3
Affiliations

Incorporating gold nanoclusters and target-directed liposomes as a synergistic amplified colorimetric sensor for HER2-positive breast cancer cell detection

Yu Tao et al. Theranostics. .

Abstract

Breast cancer is the second leading cause of cancer-related mortality in women. Successful development of sensitive nanoprobes for breast cancer cell detection is of great importance for breast cancer diagnosis and symptomatic treatment. Herein, inspired by the intrinsic peroxidase property of gold nanoclusters, high loading, and targeting ability of ErbB2/Her2 antibody functionalized liposomes, we report that gold nanoclusters-loaded, target-directed, functionalized liposomes can serve as a robust sensing platform for amplified colorimetric detection of HER2-positive breast cancer cells. This approach allows HER2-positive breast cancer cell identification at high sensitivity with high selectivity. In addition, the colorimetric "readout" offers extra advantages in terms of low-cost, portability, and easy-to-use applications. The practicality of this platform was further proved by successful detection of HER2-positive breast cancer cells in human serum samples and in breast cancer tissue, which indicated our proposed method has potential for application in cancer theranostics.

Keywords: Colorimetric sensor; artificial enzymes; breast cancer cells; gold nanoclusters; liposomes; signal amplification.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Scheme 1
Scheme 1
Schematic representation of (a) preparation of anti-HER2 conjugated liposome-AuNCs hybrid (BSA-AuNCs-LPs-anti-HER2) and (b) HER2-positive breast cancer cell detection by using BSA-AuNCs-LPs-anti-HER2.
Figure 1
Figure 1
(a, b) TEM images of the BSA-AuNCs-LPs-anti-HER2 under different magnifications; (c) SEM images of the BSA-AuNCs-LPs-anti-HER2; (d) EDS spectra of the as-synthesized BSA-AuNCs-LPs-anti-HER2.
Figure 2
Figure 2
(a) The absorbance spectra and visual color changes of TMB in different reaction systems: (1) TMB + H2O2, (2) BSA-AuNCs-LPs-anti-HER2 + TMB, and (3) BSA-AuNCs-LPs-anti-HER2 + TMB + H2O2 in PBST (25 mM Na2HPO4, pH 4.0, with 0.05% Tween-20) at 25 °C after 30 min incubation. (b) The absorbance spectra and visual color changes of TMB in presence of different concentrations of BSA-AuNCs-LPs-anti-HER2 after 30 min incubation. Inset: the absorption values at 652 nm depend on the concentrations of BSA-AuNCs-LPs-anti-HER2. (c, d) The peroxidase-like activity of the BSA-AuNCs-LPs-anti-HER2 is dependent on pH (c) and temperature (d).
Figure 3
Figure 3
HER2-positive breast cancer cell detection by using BSA-AuNCs-LPs-anti-HER2. (a) The absorbance spectra and visual color changes upon analyzing different number of SKBR3 cells. (b) The absorption values at 652 nm depend on the number of SKBR3 cells. Inset: the linear plot. The error bars represent the standard deviation of three measurements. (c-d) Selectivity analysis for HER2-positive breast cancer cell detection using BSA-AuNCs-LPs-anti-HER2 by monitoring the absorbance spectra (c) and color changes (d). The error bars represent the standard deviation of three measurements.
Figure 4
Figure 4
(a-b) HER2-positive breast cancer cell detection by using BSA-AuNCs-LPs-anti-HER2 in human serum (50%). (a) The absorbance spectra upon analyzing different number of SKBR3 cells. (b) The absorption values at 652 nm depend on the number of SKBR3 cells. Inset: the linear plot. The error bars represent the standard deviation of three measurements. (c-f) Immunohistochemistry (IHC) staining of breast cancer tissues with HER2 from 0 (c), 1+ (d), 2+ (e) and 3+ (f). Scale bar = 100 μm. (g-h) HER2-positive breast cancer tissue detection by using BSA-AuNCs-LPs-anti-HER2. The absorbance spectra response (g) and absorption values at 652 nm (h) enhanced with increase in HER2 IHC score (0, 1+, 2+, 3+).
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