Glycated chitosan as a new non-toxic immunological stimulant

Abstract

Chitosan is capable to stimulate immune responses. However, because chitosan is not water soluble, it has limited biological applications. By attaching galactose molecules to the chitosan molecules, a new water-soluble compound, glycated chitosan (GC), was synthesized. GC was designed for immune stimulations in combination with phototherapies in the treatment of metastatic tumors. To investigate the possible toxicity of GC, cultures of normal and tumor cells were incubated with GC of different concentrations and the cell viabilities were determined. For in vivo studies, GC solution was fed or injected to animals and its toxicity was determined through observations of animals and histological examinations of vital organs. No toxic effects of GC were observed in cultured cells or in animal studies. In addition, the immunological effect of GC was investigated through its stimulation of TNFα secretion by macrophages in vitro. In vivo studies showed enhancement of the survival of laser immunotherapy-treated rats bearing metastatic mammary tumors. Our in vitro and in vivo results indicated that GC was a strong immunological stimulant. Its non-toxic nature and immunological activity make GC a potential immunoadjuvant for treatment of metastatic tumors.

Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases

“…In addition, recent studies suggest that COS have potential anti-inflammatory properties in vivo and in vitro. For example, Song et al reported that COS may be a potential immunoadjuvant for the treatment of metastatic tumors [11] . In the studies…”

Laser immunotherapy for the treatment of human breast cancer: one-year follow up results

“…The pre-clinical studies showed that GC was non-toxic [10][11]. In our clinical studies, no systemic toxicity was observed following injection of GC.…”

“…The two principles underlying LIT are (1) local heating of the primary tumor with a laser (which may be combined with a light-absorbing agent to facilitate the heating) to devitalize the tumor and liberate tumor antigens, and (2) local injection of glycated chitosan (GC), a potent nontoxic immunoadjuvant that interacts with the liberated tumor antigens to induce an immune response against the cancer [10][11]. In our pre-clinical studies, we have observed the eradiation of treated primary tumors and also untreated metastatic tumors at distant sites, along with long-term, strong tumor-specific immunological responses [12][13][14][15][16].…”

Anti-tumor response induced by immunologically modified carbon nanotubes and laser irradiation using rat mammary tumor model

“…5 The immunoadjuvant glycated chitosan (GC) was formulated to enhance the activation of the immune system. 6 GC is biocompatible, water soluble, and capable of increasing the concentration of cytokines as well as activating immune cells. 7,8 Additionally, GC can be used as a surfactant.…”