Advanced nanotherapeutics inspired by the abnormal microenvironment of leukemia

During the development of leukemia, the overgrowth of leukemia cells in the bone marrow transforms the normal hematopoietic microenvironment into the leukemia microenvironment which favors its growth and inhibits normal hematopoietic stem cells. The leukemia microenvironment exhibits abnormalities in redox substances, metabolism, immune response, mesenchymal cells, extracellular matrix, stromal cells, hypoxia, and more. These factors collectively provide a shelter for the malignant proliferation of leukemia cells. Recently, as the understanding of the leukemia microenvironment deepens, targeting or remodeling the abnormal leukemia microenvironment is becoming an effective strategy for leukemia treatment. Nanomedicine technology can effectively change pharmacokinetic profiles, thus demonstrating many advantages in modulating the leukemia microenvironment and improving therapeutic selectivity. In this review, we outline the characteristics of abnormal leukemia bone marrow microenvironment, focusing on the abnormal changes in the redox, metabolic and immune microenvironment. We also summarize emerging nanotechnology strategies in remodeling or targeting the aforementioned abnormal microenvironment. In addition, the unique advantages and bright prospects of nanotechnology in remodeling and targeting the leukemia microenvironment are discussed.