Integrins in wound healing, fibrosis and tumor stroma: High potential targets for therapeutics and drug delivery

Wound healing is a complex process, which ultimately leads to fibrosis if not repaired well. Pathologically very similar to fibrosis is the tumor stroma, found in several solid tumors which are regarded as wounds that do not heal. Integrins are heterodimeric surface receptors which control various physiological cellular functions. Additionally, integrins also sense ECM-induced extracellular changes during pathological events, leading to cellular responses, which influence ECM remodeling. The purpose and scope of this review is to introduce integrins as key targets for therapeutics and drug delivery within the scope of wound healing, fibrosis and the tumor stroma. This review provides a general introduction to the biology of integrins including their types, ligands, means of signaling and interaction with growth factor receptors. Furthermore, we highlight integrins as key targets for therapeutics and drug delivery, based on their biological role, expression pattern within human tissues and at cellular level. Next, therapeutic approaches targeting integrins, with a focus on clinical studies, and targeted drug delivery strategies based on ligands are described. Existing integrin drug targeting ligands, applied for the modification of drug molecules, drug carriers and CAR-T cells (CAR-T), in the context of wound healing, fibrosis or tumor stroma and their respective integrin targets. Dashed lines show potential integrin targets for existing ligands (PHSCNK, PR_b, RGD, RKK12, quinolonic, echistatin) that have not yet been used for targeting the respective cell line. In addition to already targeted integrins, integrins that have not yet been targeted but play a role in the pathology of wound healing, fibrosis or tumor stroma are presented. [Display omitted]