Abstract

Rapid monitoring of the response to treatment in cancer patients is essential to predict the outcome of the therapeutic regimen early in the course of the treatment. The conventional methods are laborious, time-consuming, subjective and lack the ability to study different biomolecules and their interactions, simultaneously. Since; mechanisms of cancer and its response to therapy is dependent on molecular interactions and not on single biomolecules, an assay capable of studying molecular interactions as a whole, is preferred. Fourier Transform Infrared (FTIR) spectroscopy has become a popular technique in the field of cancer therapy with an ability to elucidate molecular interactions. The aim of this study, was to explore the utility of the FTIR technique along with multivariate analysis to understand whether the method has the resolution to identify the differences in the mechanism of therapeutic response. Towards achieving the aim, we utilized the mouse xenograft model of retinoblastoma and nanoparticle mediated targeted therapy. The results indicate that the mechanism underlying the response differed between the treated and untreated group which can be elucidated by unique spectral signatures generated by each group. The study establishes the efficiency of non-invasive, label-free and rapid FTIR method in assessing the interactions of nanoparticles with cellular macromolecules towards monitoring the response to cancer therapeutics.

Highlights

  • Over the last few decades, Fourier Transform Infrared ( FTIR) spectroscopy has become a popular spectroscopic technique in the field of cancer diagnosis[1,2,3]

  • We explored the utility of Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) technique to understand whether the method has the capacity to distinguish the mechanism involved in therapeutic response using nanoparticle mediated targeted therapy and retinoblastoma (RB) xenograft mouse model

  • The bands at 2914 cm−1 and 2904 cm−1 are attributed to the C-H stretch of the methylene groups of 3 mercaptopropionic acid (MPA) attached to the HDM2 peptide[24]

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Summary

Introduction

Over the last few decades, Fourier Transform Infrared ( FTIR) spectroscopy has become a popular spectroscopic technique in the field of cancer diagnosis[1,2,3]. The success of the in-situ hybridization and immunohistochemical techniques including tissue microarray rely on several physical and chemical aspects such as specificity and sensitivity of the probes and antibodies, hybridization/incubation parameters, chemical reagents used for tissue processing, labeling and detection[6,7] These diagnostic methods do not aid in studying the interaction of different biomolecules such as proteins, lipids, nucleic acids in a given sample. We have applied ATR-FTIR technique to assess the interactions of the GNPs-conjugates with the cellular macromolecules such as proteins, lipids, and nucleic acids in the tumor tissue

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