Issue 21, 2020

Polymer-loaded hydrogels serve as depots for lactate and mimic “cold” tumor microenvironments

Abstract

The burgeoning field of biomaterials for immunotherapy has aided in the understanding of foundational mechanisms of cancer immunology. In particular, implantable biomaterials can be engineered to investigate specific aspects of the tumor microenvironment either singularly or in combination. Of note, the metabolite – lactate, a byproduct of anaerobic glycolysis, is known to reprogram immune cells, resulting in increased tumor survival. An adequate model that can recapitulate intratumoral lactate concentrations does not exist. In this study, we demonstrate that a simple biomaterial platform could be developed as an instructive tool to decipher the effects of lactate in vivo. Briefly, we demonstrate that a peptide hydrogel loaded with granulocyte-macrophage colony stimulating factor and poly-(lactic-co-glycolic acid)/(lactic acid) microparticles can generate the localized lactate concentrations (∼2–22 mM) and cellular makeup of the tumor microenvironment, following subcutaneous implantation in mice. Furthermore, infiltrating immune cells adopt phenotypes similar to those seen in other in vitro and in vivo cancer models, including immunosupressive dendritic cells. This hydrogel system is a framework to interrogate immune cell modulation in cancer-like environments using safe and degradable biomaterials. Moreover, this system can be multifaceted, as incorporation of other cancer tumor environmental factors or chemotherapeutic drugs is facile and could be insightful in developing or improving immunotherapies.

Graphical abstract: Polymer-loaded hydrogels serve as depots for lactate and mimic “cold” tumor microenvironments

Supplementary files

Article information

Article type
Paper
Submitted
18 iyl 2020
Accepted
06 sen 2020
First published
18 sen 2020

Biomater. Sci., 2020,8, 6056-6068

Polymer-loaded hydrogels serve as depots for lactate and mimic “cold” tumor microenvironments

R. Allen, E. Ivtchenko, B. Thuamsang, R. Sangsuwan and J. S. Lewis, Biomater. Sci., 2020, 8, 6056 DOI: 10.1039/D0BM01196G

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