The Study Of A Novel Injectable Bioactive Hydrogel For Tumor Reversion

Recent studies have shown that embryonic tissue micro-environment could reversetumor cell malignant phenotype into normal cells through epigenetic mechanisms, whichis mainly caused by the overexpression of uncontrolled Nodal signaling protein.According to such findings, ideas of establishing the system in vitro to simulate thismicro-environment for cancer therapy have been proposed by some researchers.In this study, a kind of injectable hydrogel simulating the embryonicmicroenvironment was designed using hyluronic acid, the main components inembryonic extracellular matrix, as the basic material, which was chemically cross-linkedwith active peptide. Simultaneously, Nodal receptor, anti cripto-1antibody is grafted ontothe frame of the gel to imitate the biological environment of reversing tumor inembryonic development.We tested the properties of hydrogel including rheology, porosity, microstructuremorphology and the micro three-dimensional structure of tumor cells grown in thehydogel, which demonstrated that the hydrogel system could be used as ideal scaffoldsfor tumor reversion in vitro. Our study choose MDA-MB-231as the representative ofinvasion, MCF-7as the rapid proliferation without invasion. We confirmed the bioactivehydrogel system could reduce Mitochondrial Membrane Potential of MDA-MB-231andMCF-7, promote cell apoptosis and reduce the invasion of cells effectively in vitro. Thedegradation rate of the hydrogels in vivo was detected via small animal in vivo imagingtechnique, indicating that the gel was degraded completely10days later. These resultswere also confirmed in Nude mice model. Nude mice were injected with theexperimentally determined minimal tumor does of5×106B16cells and1×107MDA-MB-231cells. After developing into palpable tumor, the gel was injected into thetumor site, solidifying into an insoluble gel, and the grafted antibody will be releasedfrom the gel, so as to form the local environment to reverse tumor malignant phenotype.The results show that the hydrogel system can significantly reduce the tumor volume ofMDA-MB-231cells, some tumor even disappeared after the treatment for45days later.Futhermore, the gel could effectively inhibit the growth of highly malignant B16tumor.Our study aims to triturate a new type of bioactivity hydrogel used for the reversetransformation of the tumor, which may be useful to design novel therapeuticintervention strategies for cancers.