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Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy: An analytical technique to understand therapeutic responses at the molecular level.

Kalmodia S, Parameswaran S, Yang W, Barrow CJ, Krishnakumar S - Sci Rep (2015)

Bottom Line: Fourier Transform Infrared (FTIR) spectroscopy has become a popular technique in the field of cancer therapy with an ability to elucidate molecular interactions.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nano biotechnology, Vision Research Foundation, Sankara Nethralaya, 18, College Road, Nungambakkam, Chennai - 600 006, India.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of GNP conjugates on the xenograft model.The control, GNPs-1 and GNPs-2 mice were monitored every three days till 24th day for tumor growth (tumor volume measured using caliper) and body weight. The relative tumor volume (RTV) and tumor growth inhibition were calculated. Mean ± SEM was calculated for the RTV data and tumor growth inhibition was presented as a percentage. Two way ANOVA was utilized for statistical analysis and p value <0.05 was considered significant. RTV (A) and TGI (B) showed statistically significant difference between the control and the treated groups (p < 0.0001). Analysis of the body weight in grams revealed that the body weight of the mice did not significantly differ between different groups throughout the treatment (p = 0.0938; Two way ANOVA) (C).
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f2: Effect of GNP conjugates on the xenograft model.The control, GNPs-1 and GNPs-2 mice were monitored every three days till 24th day for tumor growth (tumor volume measured using caliper) and body weight. The relative tumor volume (RTV) and tumor growth inhibition were calculated. Mean ± SEM was calculated for the RTV data and tumor growth inhibition was presented as a percentage. Two way ANOVA was utilized for statistical analysis and p value <0.05 was considered significant. RTV (A) and TGI (B) showed statistically significant difference between the control and the treated groups (p < 0.0001). Analysis of the body weight in grams revealed that the body weight of the mice did not significantly differ between different groups throughout the treatment (p = 0.0938; Two way ANOVA) (C).

Mentions: All the mice in the control and the treated groups survived until the end of the analysis. The mean body weight of the control, GNP1 and GNP2 treated groups at the beginning of the treatment (Day 0) were 19.82 ± 0.48, 21.06 ± 0.81 and 20.33 ± 0.46, respectively. No significant differences in the body weight were observed between the control and different treatment groups throughout the experiment (p = 0.9988; Two way ANOVA) (Fig. 2C). Analysis of the liver function (ALT, AST) and kidney function (Creatinine, BUN) tests revealed that the GNP conjugates were non- toxic to the vital organs (Supplementary Fig S3 A-D). The histopathological analysis of liver, lung, spleen, heart and kidney in all the groups appeared normal, substantiating the dose tolerance and non-toxic nature of the treatments (Supplementary Fig S4). The DLC revealed no significant changes in the percentage of eosinophils, monocytes, lymphocytes and neutrophils compared to the controls suggesting the absence of bone marrow suppression (Supplementary Fig S3E). The analysis of the relative tumor volume and tumor growth inhibition revealed that both the GNPs-1 and GNPs-2 treatment led to a statistically significant difference in the tumor reduction compared to the control (p < 0.0001; Two-way ANOVA) (Fig. 2A,B). The tumor growth inhibition at the end of 24 days were 18% and 28% in the GNPs-1 and GNPs-2 (p < 0.001) treated groups, respectively.


Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy: An analytical technique to understand therapeutic responses at the molecular level.

Kalmodia S, Parameswaran S, Yang W, Barrow CJ, Krishnakumar S - Sci Rep (2015)

Effect of GNP conjugates on the xenograft model.The control, GNPs-1 and GNPs-2 mice were monitored every three days till 24th day for tumor growth (tumor volume measured using caliper) and body weight. The relative tumor volume (RTV) and tumor growth inhibition were calculated. Mean ± SEM was calculated for the RTV data and tumor growth inhibition was presented as a percentage. Two way ANOVA was utilized for statistical analysis and p value <0.05 was considered significant. RTV (A) and TGI (B) showed statistically significant difference between the control and the treated groups (p < 0.0001). Analysis of the body weight in grams revealed that the body weight of the mice did not significantly differ between different groups throughout the treatment (p = 0.0938; Two way ANOVA) (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645174&req=5

f2: Effect of GNP conjugates on the xenograft model.The control, GNPs-1 and GNPs-2 mice were monitored every three days till 24th day for tumor growth (tumor volume measured using caliper) and body weight. The relative tumor volume (RTV) and tumor growth inhibition were calculated. Mean ± SEM was calculated for the RTV data and tumor growth inhibition was presented as a percentage. Two way ANOVA was utilized for statistical analysis and p value <0.05 was considered significant. RTV (A) and TGI (B) showed statistically significant difference between the control and the treated groups (p < 0.0001). Analysis of the body weight in grams revealed that the body weight of the mice did not significantly differ between different groups throughout the treatment (p = 0.0938; Two way ANOVA) (C).
Mentions: All the mice in the control and the treated groups survived until the end of the analysis. The mean body weight of the control, GNP1 and GNP2 treated groups at the beginning of the treatment (Day 0) were 19.82 ± 0.48, 21.06 ± 0.81 and 20.33 ± 0.46, respectively. No significant differences in the body weight were observed between the control and different treatment groups throughout the experiment (p = 0.9988; Two way ANOVA) (Fig. 2C). Analysis of the liver function (ALT, AST) and kidney function (Creatinine, BUN) tests revealed that the GNP conjugates were non- toxic to the vital organs (Supplementary Fig S3 A-D). The histopathological analysis of liver, lung, spleen, heart and kidney in all the groups appeared normal, substantiating the dose tolerance and non-toxic nature of the treatments (Supplementary Fig S4). The DLC revealed no significant changes in the percentage of eosinophils, monocytes, lymphocytes and neutrophils compared to the controls suggesting the absence of bone marrow suppression (Supplementary Fig S3E). The analysis of the relative tumor volume and tumor growth inhibition revealed that both the GNPs-1 and GNPs-2 treatment led to a statistically significant difference in the tumor reduction compared to the control (p < 0.0001; Two-way ANOVA) (Fig. 2A,B). The tumor growth inhibition at the end of 24 days were 18% and 28% in the GNPs-1 and GNPs-2 (p < 0.001) treated groups, respectively.

Bottom Line: Fourier Transform Infrared (FTIR) spectroscopy has become a popular technique in the field of cancer therapy with an ability to elucidate molecular interactions.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nano biotechnology, Vision Research Foundation, Sankara Nethralaya, 18, College Road, Nungambakkam, Chennai - 600 006, India.

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.

No MeSH data available.


Related in: MedlinePlus