Assessment of cellular response to drug/nanoparticles conjugates treatment through FTIR imaging and PLS regression study

Abstract

This work explores the potential of Fourier transform infrared (FTIR) spectroscopic imaging at the single-cell level combined with partial least squares (PLS) regression to investigate the cell’s response to drug/gold nanoparticles (AuNPs) conjugates. In a broader context, this study provides not only the effective differentiation between non-tumorigenic, mildly malignant and malignant cells, but above all proposes a novel approach to define the sensitivity of cancer cells to drugs. AuNPs can be widely and effectively used in biosensing and bioimaging applications. Three human breast cell lines, i.e. MCF10A (non-tumorigenic), MCF7 (metastatic, pleural effusion, mildly malignant) and MDA-MB-231 (metastatic, pleural effusion, malignant) have been exposed to different concentration of AuNPs (15 mg/L and 10 mg/L) and AuNPs/α-methyl-DL-tryptophan conjugates conjugates (10 mg/L NPs @ 3.75 × 10−6 M and 10 mg/L NPs @ 3.75 × 10−5 M). It is implied that the class values predicted by the PLS regression model indicate a very good separation between non-tumorigenic, mildly malignant and malignant cells. Furthermore, the FTIR-PLS approach shows that bands responsible for the segregation between the control cells and the cells treated with drug/AuNPs conjugate result from the changes in RNA/DNA, lipids and amide I and II vibrations. Drug/AuNPs conjugate affects the nucleic acids in all of the studied cell types. The performed analysis suggests that MCF-7 cell line is particularly sensitive to the drug treatment, which result in the drug interacting with nucleic acids and DNA conformational changes.