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

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Polymer-loaded hydrogels serve as depots for lactate and mimic “cold” tumor microenvironments
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-09-18 , DOI: 10.1039/d0bm01196g
Riley Allen ₁ , Emilie Ivtchenko , Bhasirie Thuamsang , Rapeepat Sangsuwan , Jamal S Lewis

Affiliation

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.

中文翻译：

聚合物负载水凝胶可作为乳酸的储存库并模拟“冷”肿瘤微环境

新兴的免疫治疗生物材料领域有助于理解癌症免疫学的基本机制。特别是，可植入生物材料可以设计成单独或组合研究肿瘤微环境的特定方面。值得注意的是，代谢物乳酸是无氧糖酵解的副产物，已知可以重新编程免疫细胞，从而增加肿瘤存活率。不存在可以概括肿瘤内乳酸浓度的适当模型。在这项研究中，我们证明可以开发一个简单的生物材料平台作为破译乳酸在体内的影响的指导工具。简而言之，我们证明了装载有粒细胞 - 巨噬细胞集落刺激因子和聚（乳酸 -共-glycolic酸）/（乳酸）微粒可以生成局部乳酸浓度（~2-22毫摩尔）和肿瘤微环境的蜂窝妆，在小鼠皮下植入。此外，浸润免疫细胞采用与其他体外和体内癌症模型（包括免疫抑制树突状细胞）中所见相似的表型。该水凝胶系统是使用安全且可降解的生物材料在类似癌症的环境中询问免疫细胞调节的框架。此外，该系统可以是多方面的，因为结合其他癌症肿瘤环境因素或化学治疗药物很容易，并且可以在开发或改进免疫疗法方面具有洞察力。

更新日期：2020-10-02

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