Mutual influence of malignant cells and cellular microenvironment: prospects for manipulating tumour microenvironment with nanomaterials

Abstract

Development and progression of neoplasia occurs in parallel with changes in the surrounding stroma. Cancer cells may functionally reshape their microenvironment by secreting various cytokines, chemokines and generation of acidic medium. These factors contribute to differentiation of immune cells into immunosuppressive phenotype, stimulate the synthesis of a number of amino acid metabolism enzymes, growth factors, adhesion molecules, which promote invasion, angiogenesis and metastasis, and also reduce efficiency of anticancer drugs and radiation therapy. To increase effectiveness of the chemotherapy, multitargeted carbon nanomaterials may be applied. In particular, nanomaterials based on modified graphene make it possible to create multicomponent therapeutic constructs, including macromolecules, polymers, and effector agents. Initial experiments with unmodified graphenes demonstrated their toxicity associated with their accumulation in parenchymal organs and initiation of inflammatory processes. In the past few years, a series of works has been published in which the possibility of reducing the toxicity of graphene oxide through functionalisation has been demonstrated. This review summarises the experimental data on the creation of covalent and non-covalent conjugates based on graphene oxide and demonstrates their in vitro efficacy on various tumour cell lines. Separately, there are few data on the effect of nanomaterials based on graphene oxide on the tumour microenvironment.