Engineering of thermoresponsive gels as a fake metastatic niche

Abstract

Chemoattraction through the CXCR4-CXCL12 axis has been shown to be an important mechanism to direct circulating tumor cells toward distant sites. The objective of this work was to prepare a fake metastatic niche made up of a gel loaded with CXCL12. The gel is designed to create a steep concentration gradient of the chemokine in the proximity of the site of administration/injection, aimed to divert and capture circulating CXCR4⁺ tumor cells. To this aim, different thermoresponsive gels based on methylcellulose (MC) or poloxamers, loaded with CXCL12, with or without hyaluronic acid (HA) were designed and their mechanical properties correlated with the ability to attract and capture in vitro CXCR4⁺ cells. Results of in vitro cell studies showed that all prepared gels induced CEM tumor cell migration whereas only gels based on MC embedded with CXCL12 are able to capture them.

Keywords: CEM cells; CXCL12-CXCR4 axis; Metastasis trap; Thermosensitive gel.