Identification of a Profile of Neutrophil-Derived Granule Proteins in the Surface of Gold Nanoparticles after Their Interaction with Human Breast Cancer Sera.

María Del Pilar Chantada-Vázquez,Sergio Vázquez-Estévez,Susana B Bravo,Cristina Núñez,María García-Vence

doi:10.3390/nano10061223

Abstract

It is well known that the interaction of a nanomaterial with a biological fluid leads to the formation of a protein corona (PC) surrounding the nanomaterial. Using standard blood analyses, alterations in protein patterns are difficult to detect. PC acts as a “nano-concentrator” of serum proteins with affinity for nanoparticles’ surface. Consequently, characterization of PC could allow detection of otherwise undetectable changes in protein concentration at an early stage of a disease, such as breast cancer (BC). Here, we employed gold nanoparticles (AuNPsdiameter: 10.02 ± 0.91 nm) as an enrichment platform to analyze the human serum proteome of BC patients (n = 42) and healthy controls (n = 42). Importantly, the analysis of the PC formed around AuNPs after their interaction with serum samples of BC patients showed a profile of proteins that could differentiate breast cancer patients from healthy controls. These proteins developed a significant role in the immune and/or innate immune system, some of them being neutrophil-derived granule proteins. The analysis of the PC also revealed serum proteome alterations at the subtype level.

Highlights

Breast cancer (BC) rises to 1.4 million new cases worldwide each year [1]
Due to the colloidal stability, the high surface-area-to-volume ratio and the ability to conjugate with biomolecules [32], gold nanoparticles (AuNPs: 10.02 ± 0.91 nm) were used to incubate with serum samples of breast cancer patients and healthy controls, and the resultant protein coronas were thoroughly characterized and compared by mass spectrometry (MS)-based proteomics
We used AuNPs (10.02 ± 0.91 nm) to pre-concentrate low-abundance proteins presented in the sera of breast cancer patients (BC) patients (n = 42) and healthy controls (n = 42), and the resultant protein coronas were thoroughly characterized to identify potential protein biomarkers

Summary

Introduction

BC is currently classified into five intrinsic subtypes, that have been defined as follows: (1) luminal A subtype or LA (estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, Ki-67 cell proliferation marker low, and progesterone receptor (PR) high); (2) luminal B-HER2 negative or LB− (ER positive, HER2 negative, and either Ki-67 high or PR low); (3) luminal B-HER2 positive or LB+ (ER positive, HER2 overexpressed or amplified, any Ki-67, and any PR); (4) HER2 positive or HER2+ (HER2 over-expressed or amplified, ER and PR absent); and (5) triple negative breast cancer or TNBC (ER and PR absent and HER2 negative) [3]. Proteomics might identify protein biomarkers defining differences in prognosis, therapy resistance and metastatic spread within a specific subtype

Methods

Results

Conclusion