Self-assembled fructo-oligosaccharide conjugated ferulic acid microparticle: Anticancer, anti-inflammatory and immunomodulatory effects

Abstract

Fructo-oligosaccharide ferulic acid conjugate was synthesized, which self-assembles into disc shaped amorphous microparticles (FA FOS I), that could be used for targeted delivery to the colon. It is accessed for its ability to ameliorate colorectal cancer and inflammation. The microparticle exhibited selective cytotoxicity and apoptosis induction in colon cancer cells. The microparticle arrested the cell cycle in the G0-G1 phase. In-vivo anti-colorectal cancer activity were evaluated in colitis associated colon cancer mice model. There was a reduction in 60.83% of tumour lesions and 48.27% reduction in the malignant cells. The immunohistochemistry (IHC) revealed the suppression of inflammation and related inflammatory cytokines in the colon. The inhibition of cell proliferation, up-regulation of tumour suppressor protein and induction of apoptosis in the malignant cells were observed. The evaluation of immune modulation by FA FOS I microparticle revealed a 9% increase in WBC count and an increase in the infiltration of T-helper cells and cytotoxic T-cells into the tumour microenvironment. There was a considerable decrease in the expression of immune suppressing PD-L1 by the tumour cells on treatment with FA FOS I microparticle. All these data implicate better efficacy of the FA FOS I microparticle delivery to colon and amelioration of colitis associated colorectal cancer through multimodal route of inflammation reduction, apoptosis induction and positive modulation of immune system in the tumour microenvironment. FA FOS I was proposed to be a candidate drug which is physiologically and metabolically stable under gastro-intestinal condition and potentiating its effect in the target site large intestine; without being absorbed or transported to other tissue nor causing any adverse cytotoxicity to the neighbouring normal tissue.