Introduction – Butyrate is a short-chain fatty acid produced from microbial fermentation of dietary fibre in the human large intestine that inhibits proliferation, induces apoptosis and downregulates metabolic activity in colorectal cancer cells, while aiding healthy colonocyte function (1). Oral and peripheral administrations of butyrate are limited by its short half-life (5min), ubiquitous nature, first-pass hepatic clearance and toxic dose. The objective of the present study is to evaluate the therapeutic potential of liposome-encapsulated butyrate for the treatment of colorectal cancer using bioluminescence imaging (BLI), tumour volume changes and ex vivo histological analysis. Methods – Liposomes were formulated using a defined ratio of selected lipids (patent CA2882705A1)(2). Lipids dissolved in chloroform were dried in vacuo at 30oC using a rotary evaporator (Bucchi, UK) and hydrated using sodium butyrate (1M). Liposomes (100-150nm) were formed through ultrasonication (Fisher Scientific, UK) and sized using dynamic light scattering (DLS) (Malvern, UK). Non-encapsulated drug was removed by dialysis against a saline buffer solution (1M NaCl). Encapsulation efficiency was calculated using nuclear magnetic resonance (NMR) (400MHz; Bruker, UK). Human LS174T colorectal adenocarcinoma cells were transfected with the firefly luciferase gene (LS174T_Luc+). Mice bearing LS174T-Luc+ subcutaneous tumours were chronically treated (3 times/week) with liposomes encapsulating butyrate or water (control) for 3 weeks (n=14). Tumour growth was tracked using BLI (luciferin 15mg/ml) and calliper-derived volumes. After therapy, mice were perfusion-fixed and tissues of interest were histologically analysed. Results – The BLI data showed a significant decrease in BLI signal in butyrate treated tumours compared to controls within the first 10 days of treatment (Fig. 1; p<0.05). There were no significant differences in tumour volumes between groups, suggesting that metabolic downregulation in tumours does not directly correlate to tumour size. Conclusions – This study is the first to evaluate the effect of liposomal butyrate on colorectal cancer in vivo using BLI. Since the production of photons from the catalysis of luciferin is dependent on adenosine triphosphate (ATP), the BLI data indicates that butyrate compromises the production of cellular energy thereby inducing metabolic downregulation in colorectal tumours. The fact that simultaneously tumour size was not significantly altered demonstrates the importance of evaluating therapeutic outcomes in vivo through non-invasive imaging methods. The present data promotes further evaluation of liposomal butyrate therapy, while its lack of toxicity highlights its potential as a preventive, pre-diagnostic and adjuvant treatment of colorectal cancer.